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Candidate list of top vitamin D papers for 2012

By William B. Grant, et al. Dec 25, 2012

This list has about 56 papers. I would like to get it down to 10-12 or so.
The papers included should be important to the general population.
They should also cover a range of topics related to vitamin D.

CLICK HERE for the winners

Short list of papers - followed by abstracts

Some fraction of the papers have web pages on VitaminDWiki

Asthma

  • Bener A, Ehlayel MS, Tulic MK, Hamid Q. Vitamin D deficiency as a strong predictor of asthma in children. . 2012;157(2):168-75.

Autism

  • Kočovská E, Fernell E, Billstedt E, Minnis H, Gillberg C. Vitamin D and autism: clinical review. . 2012 Sep-Oct;33(5):1541-50.
  • Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM. Maternal Vitamin D Levels and the Autism Phenotype Among Offspring. . 2012 Oct 16. [Epub ahead of print]

Cancer

  • Lin SW, Wheeler DC, Park Y, Cahoon EK, Hollenbeck AR, Michal Freedman D, Abne CC. Prospective study of ultraviolet radiation exposure and risk of cancer in the U.S. Int J Cancer. 2012 Sep 15;131(6):E1015-23.
  • Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Host RL, Ambrose LH, Kindy MS, Gattoni-Celli S. Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance. J Clin Endocrinol Metab. 2012 Jul;97(7):2315-24.
  • Tretli S, Schwartz GG, Torjesen PA, Robsahm TE. Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study. . 2012 Feb;23(2):363-70.

Cardiovascular disease

  • Brøndum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M. 25-Hydroxyvitamin D and symptomatic ischemic stroke: An Original Study and Meta-Analysis. . 2012 Aug 25. doi: 10.1002/ana.23738. [Epub ahead of print]
  • Chowdhury R, Stevens S, Ward H, Chowdhury S, Sajjad A, Franco OH. Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis. . 2012 Aug;27(8):581-91.
  • Liu L, Chen M, Hankins SR, Nùñez AE, Watson RA, Weinstock PJ, Newschaffer CJ, Eisen HJ; Drexel Cardiovascular Health Collaborative Education, Research, and Evaluation Group. Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from all-cause in United States adults. . 2012 Sep 15;110(6):834-9.
  • Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12 000 deaths. . 2012 Dec 20. [Epub ahead of print]
  • Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA. Vitamin D deficiency and supplementation and relation to cardiovascular health. . 2012 Feb 1;109(3):359-63.
  • Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C, Eaton CB, May HT, Anderson JL, Sesso HD. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: A meta-analysis of prospective studies. . 2012 Nov 1;5(6):819-29.

Cognitive function, dementia

  • Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. . 2012 Sep 25;79(13):1397-405.
  • Slinin Y, Paudel M, Taylor BC, Ishani A, Rossom R, Yaffe K, Blackwell T, Lui LY, Hochberg M, Ensrud KE; Study of Osteoporotic Fractures Research Group. Association between serum 25(OH) vitamin D and the risk of cognitive decline in older women. . 2012 Oct;67(10):1092-8.

Dental caries

  • Hujoel PP. Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis. Nutrition Reviews. 2012

Depression

  • Jaddou HY, Batieha AM, Khader YS, Kanaan SH, El-Khateeb MS, Ajlouni KM. Depression is associated with low levels of 25-hydroxyvitamin D among Jordanian adults: results from a national population survey. . 2012 Jun;262(4):321-7.

Development

  • Villamor E, Marin C, Mora-Plazas M, Baylin A. Vitamin D deficiency and age at menarche: a prospective study. . 2011 Oct;94(4):1020-5.

Diabetes mellitus, type 1

  • Gorham ED, Garland CF, Burgi AA, Mohr SB, Zeng K, Hofflich H, Kim JJ, Ricordi C. Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring diabetes: a nested case-control study. . 2012 Dec;55(12):3224-7.

Diabetes mellitus, type 2

  • Afzal S, Bojesen SE, Nordestgaard BG. Low 25-hydroxyvitamin D and risk of type 2 diabetes: A prospective cohort study and meta-analysis. . 2012 Dec 11. [Epub ahead of print]
  • Forouhi NG, Ye Z, Rickard AP, Khaw KT, Luben R, Langenberg C, Wareham NJ. Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. . 2012 Aug;55(8):2173-82.
  • González-Molero I, Rojo-Martínez G, Morcillo S, Gutiérrez-Repiso C, Rubio-Martín E, Almaraz MC, Olveira G, Soriguer F. Vitamin D and incidence of diabetes: a prospective cohort study. . 2012 Aug;31(4):571-3.
  • Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM, Hu FB, Dawson-Hughes B; Diabetes Prevention Program Research Group. Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. . 2012 Mar;35(3):565-73.

Eyes

  • Lee V, Rekhi E, Hoh Kam J, Jeffery G. Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function. . 2012 Oct;33(10):2382-9.

Fractures

  • Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stähelin HB, Theiler R, Dawson-Hughes B. A pooled analysis of vitamin D dose requirements for fracture prevention. . 2012 Jul 5;367(1):40-9.

HIV

  • Kwan CK, Eckhardt B, Baghdadi J, Aberg JA. Hyperparathyroidism and complications associated with vitamin D deficiency in HIV-infected adults in New York City, New York. . 2012 Sep;28(9):1025-32.

Infections

  • Camargo CA Jr, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K, Sumberzul N, Rich-Edwards JW. Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. . 2012 Sep;130(3):e561-7.

Metabolic syndrome

  • Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, Sikaris K, Ebeling PR, Daly RM. Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: Results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab). . 2012 Jun;97(6):1953-61.

Mortality rate

  • Liu L, Chen M, Hankins SR, Nùñez AE, Watson RA, Weinstock PJ, Newschaffer CJ, Eisen HJ; Drexel Cardiovascular Health Collaborative Education, Research, and Evaluation Group. Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from all-cause in United States adults. . 2012 Sep 15;110(6):834-9.
  • Schöttker B, Ball D, Gellert C, Brenner H. Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies. . 2012 Feb 16. [Epub ahead of print] (in print in January)
  • Signorello LB, Han X, Cai Q, Cohen SS, Cope EL, Zheng W, Blot WJ. A prospective study of serum 25-hydroxyvitamin D levels and mortality among African Americans and non-African Americans. . 2012 Nov 1. [Epub ahead of print]
  • Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12 000 deaths. . 2012 Dec 20. [Epub ahead of print]

Muscles

  • Close GL, Russell J, Cobley JN, Owens DJ, Wilson G, Gregson W, Fraser WD, Morton JP. Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function. . 2012 Oct 22. [Epub ahead of print]
  • Girgis CM, Clifton-Bligh RJ, Hamrick MW, Holick MF, Gunton JE. The Roles of Vitamin D in Skeletal Muscle: Form, Function, and Metabolism. . 2012 Nov 20. [Epub ahead of print]

Policy

  • Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM. Vitamin D metabolism, functions and needs: from science to health claims. . 2012 Aug 12. [Epub ahead of print]
  • Hossein-nezhad A, Holick MF. Optimize dietary intake of vitamin D: an epigenetic perspective. . 2012 Nov;15(6):567-79.
  • Pérez-López FR, Brincat M, Erel CT, Tremollieres F, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K, Vujovic S, Rozenberg S, Rees M. EMAS position statement: Vitamin D and postmenopausal health. . 2012 Jan;71(1):83-8.
  • Sanders KM, Nicholson GC, Ebeling PR. Is high dose vitamin D harmful? . 2012 Dec 19. [Epub ahead of print]

Pregnancy

  • Dawodu A, Wagner CL. Prevention of vitamin D deficiency in mothers and infants worldwide - a paradigm shift. . 2012 Feb;32(1):3-13.
  • Gernand AD, Simhan HN, Klebanoff MA, Bodnar LM. Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study. . 2012 Nov 16. [Epub ahead of print]
  • Hollis BW, Wagner CL. Vitamin D and Pregnancy: Skeletal Effects, Nonskeletal Effects, and Birth Outcomes. . 2012 May 24. [Epub ahead of print]
  • Morales E, Guxens M, Llop S, Rodríguez-Bernal CL, Tardón A, Riaño I, Ibarluzea J, Lertxundi N, Espada M, Rodriguez A, Sunyer J; on behalf of the INMA Project. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics. 2012 Oct;130(4):e913-e920.
  • Principi N, Bianchini S, Baggi E, Esposito S. Implications of maternal vitamin D deficiency for the fetus, the neonate and the young infant. . 2012 Dec 9. [Epub ahead of print]
  • Wagner CL, McNeil R, Hamilton SA, Winkler J, Rodriguez Cook C, Warner G, Bivens B, Davis DJ, Smith PG, Murphy M, Shary JR, Hollis BW. A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. . 2012 Nov 3. doi:pii: S0002-9378(12)02035-2. 10.1016/j.ajog.2012.10.888. [Epub ahead of print]
  • Wagner CL, Taylor SN, Dawodu A, Johnson DD, Hollis BW. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. . 2012 Mar;4(3):208-30.
  • Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. . 2012 Mar;129(3):485-93.

Reproduction

  • Blomberg Jensen M. Vitamin D metabolism, sex hormones, and male reproductive function. . 2012 Aug;144(2):135-52.
  • Lee DM, Tajar A, Pye SR, Boonen S, Vanderschueren D, Bouillon R, O'Neill TW, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Wu FC; EMAS study group. Association of hypogonadism with vitamin D status: the European Male Ageing Study. . 2012 Jan;166(1):77-85.

Review

  • Boucher BJ. The problems of vitamin D insufficiency in older people. . 2012 Aug;3(4):313-29.

Rheumatoid arthritis

  • Song GG, Bae SC, Lee YH. Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. . 2012 Dec;31(12):1733-9.

Skin

  • Bikle DD. Protective actions of vitamin D in UVB induced skin cancer. . 2012 Nov 19;11(12):1808-16.
  • Gordon-Thomson C, Gupta R, Tongkao-On W, Ryan A, Halliday GM, Mason RS. 1α,25 Dihydroxyvitamin D(3) enhances cellular defences against UV-induced oxidative and other forms of DNA damage in skin. Photochem Photobiol Sci. 2012 Nov 19;11(12):1837-47.
  • Jablonski NG, Chaplin G. Human skin pigmentation, migration and disease susceptibility. Philos Trans R Soc Lond B Biol Sci. 2012 Mar 19;367(1590):785-92.
  • Jablonski NG. The evolution of human skin colouration and its relevance to health in the modern world. J R Coll Physicians Edinb. 2012 Mar;42(1):58-63.

Testing

  • Bailey BA, Manning T, Peiris AN. Vitamin D testing patterns among six Veterans Medical Centers in the southeastern United States: links with medical costs. Mil Med. 2012 Jan;177(1):70-6. 25(OH)D concentrations

25(OH)D concentrations

  • Luxwolda MF, Kuipers RS, Kema IP, Janneke Dijck-Brouwer DA, Muskiet FA. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr. 2012 Nov;108(9):1557-61.
  • Luxwolda MF, Kuipers RS, Kema IP, van der Veer E, Dijck-Brouwer DA, Muskiet FA. Vitamin D status indicators in indigenous populations in East Africa. Eur J Nutr. 2012 Aug 10. Epub ahead of print
  • Merewood A, Mehta SD, Grossman X, Chen TC, Mathieu J, Holick MF, Bauchner H. Vitamin D status among 4-month-old infants in New England: a prospective cohort study. J Hum Lact. 2012 May;28(2):159-66.
  • Wahl DA, Cooper C, Ebeling PR, Eggersdorfer M, Hilger J, Hoffmann K, Josse R, Kanis JA, Mithal A, Pierroz DD, Stenmark J, Stöcklin E, Dawson-Hughes B. A global representation of vitamin D status in healthy populations. Arch Osteoporos. 2012 Dec;7(1-2):155-72.

Abstracts

Reproduction. 2012 Aug;144(2):135-52. doi: 10.1530/REP-12-0064. Epub 2012 May 25.

Vitamin D metabolism, sex hormones, and male reproductive function.

Blomberg Jensen M.
Source
University Department of Growth and Reproduction, Rigshospitalet, Section 5064, Blegdamsvej 9, 2100 Copenhagen, Denmark. blombergjensen at gmail.com
Abstract
The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

J Hum Lact. 2012 May;28(2):159-66. doi: 10.1177/0890334411434802.

Vitamin D status among 4-month-old infants in New England: a prospective cohort study.

Merewood A, Mehta SD, Grossman X, Chen TC, Mathieu J, Holick MF, Bauchner H.
Source
Division of General Pediatrics, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 02118, USA. anne.merewood at bmc.org
Abstract
BACKGROUND:
Concerns over vitamin D deficiency in infants and children recently prompted the American Academy of Pediatrics to recommend increased supplementation. Few studies have examined vitamin D status in the same infants over time. Also, while many researchers label "breastfeeding" as a risk factor for vitamin D deficiency, few differentiate between any breastfeeding, exclusive breastfeeding, and supplemented or unsupplemented breastfeeders.
OBJECTIVE:
To determine predictors of 25(OH)D deficiency at 4 months in a group of children previously tested at birth.
METHODS:
We enrolled newborns from 2005 to 2007 at an urban Boston hospital. Maternal and infant blood samples were collected within 72 hours of birth. At 4 months, we obtained a second infant blood sample.
RESULTS:
At 4 months, 11.9% of the 177 infants were vitamin D deficient compared to 37.5% at birth (25(OH)D <20 ng/mL). Median 25(OH)D was 35.2 ng/mL (range, 5-100.8; 95% confidence interval [CI], 32.8-37.6). At 4 months, 40% of unsupplemented infants were deficient. Lack of supplementation was significantly associated with increased risk of deficiency (adjusted odds ratio [AOR], 19.3; 95% CI, 4.80-77.2). Being outside at least 10 minutes a day, once per week, was protective (AOR, 0.12; 95% CI, 0.02-0.66), as was increasing gestational age (AOR, 0.36; 95% CI, 0.19-0.69). In 48.4% of patients, physicians failed to prescribe vitamin D at 2 months.
CONCLUSIONS:
Despite inconsistent supplementation, a smaller proportion of infants were vitamin D deficient at 4 months than at birth. While supplemented breastfed infants were not at risk of deficiency, unsupplemented exclusively breastfed infants were at high risk of severe deficiency.

Arch Osteoporos. 2012 Dec;7(1-2):155-72. doi: 10.1007/s11657-012-0093-0. Epub 2012 Aug 29.

A global representation of vitamin D status in healthy populations.

Wahl DA, Cooper C, Ebeling PR, Eggersdorfer M, Hilger J, Hoffmann K, Josse R, Kanis JA, Mithal A, Pierroz DD, Stenmark J, Stöcklin E, Dawson-Hughes B.
Source
International Osteoporosis Foundation, Nyon, Switzerland.
Abstract
PURPOSE:
This paper visualizes the available data on vitamin D status on a global map, examines the existing heterogeneities in vitamin D status and identifies research gaps.
METHODS:
A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011. Studies were eligible if they included samples of randomly selected males and females from the general population and assessed circulating 25-hydroxyvitamin D [25(OH)D] levels. Two different age categories were selected: children and adolescents (1-18 years) and adults (>18 years). Studies were chosen to represent a country based on a hierarchical set of criteria.
RESULTS:
In total, 200 studies from 46 countries met the inclusion criteria, most coming from Europe. Forty-two of these studies (21 %) were classified as representative. In children, gaps in data were identified in large parts of Africa, Central and South America, Europe, and most of the Asia/Pacific region. In adults, there was lack of information in Central America, much of South America and Africa. Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L.
CONCLUSIONS:
This study provides an overview of 25(OH)D levels around the globe. It reveals large gaps in information in children and adolescents and smaller but important gaps in adults. In view of the importance of vitamin D to musculoskeletal growth, development, and preservation, and of its potential importance in other tissues, we strongly encourage new research to clearly define 25(OH)D status around the world.


Eur J Epidemiol. 2012 Aug;27(8):581-91. doi: 10.1007/s10654-012-9729-z. Epub 2012 Sep 9.

Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis.

Chowdhury R, Stevens S, Ward H, Chowdhury S, Sajjad A, Franco OH.
Source
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Abstract
Available literature suggests that both vitamin D and calcium may be associated with a wide range of non-skeletal outcomes. However, epidemiological evidence supporting their individual associations with incident cerebrovascular disease is scarce. We conducted a systematic review and meta-analysis of prospective cohort studies, published before February 2012 and sought from MEDLINE, EMBASE, BIOSIS and the Science Citation Index databases, and reported cerebrovascular disease (defined as any fatal or non-fatal ischemic stroke, hemorrhagic stroke, cerebrovascular accident or transient ischemic attack) by circulating vitamin D (25-hydroxy vitamin D [25(OH)D] as active metabolite) and calcium levels. Two independent investigators abstracted information on 25(OH)D and calcium, cerebrovascular outcomes and other characteristics from selected studies. Relative risks (RRs) were pooled by both random and fixed effects meta-analyses and were further examined under different study-level characteristics. Publication bias was assessed with funnel plots and Egger's asymmetry test. From 5,778 initial references, nine unique prospective cohort studies met our inclusion criteria. Seven studies (involving 47,809 participants and 926 cerebrovascular events) focused on circulating 25(OH)D and 3 reported on circulating calcium (22,577 participants and 727 events). For 25(OH)D, in a comparison of individuals in the top third versus those in the bottom third at baseline, the combined RR for cerebrovascular disease, adjusted for several conventional risk factors, was 0.60 (95 % CI 0.48, 0.72). The corresponding RR in the prospective studies that reported on baseline circulating calcium levels for cerebrovascular disease was 1.40 (95 % CI 1.19, 1.64). There was no apparent evidence of heterogeneity or publication bias among included studies. Available data indicate that higher circulating level of vitamin D is associated with a decreased risk of cerebrovascular disease. Conversely, higher circulating calcium concentration is associated with an increased risk of cerebrovascular disease.

Photochem Photobiol Sci. 2012 Nov 19;11(12):1808-16. doi: 10.1039/c2pp25251a.

Protective actions of in UVB induced skin cancer.

Bikle DD.
Source
Departments of Medicine and Dermatology, San Francisco VA Medical Center and University of California, San Francisco, CA, USA. daniel.bikle at ucsf.edu.
Abstract
Non-melanoma skin cancers (NMSC) are the most common type of cancer, occurring at a rate of over 1 million per year in the United States. Although their metastatic potential is generally low, they can and do metastasize, especially in the immune compromised host, and their surgical treatment is often quite disfiguring. Ultraviolet radiation (UVR) as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVR is also required for synthesis in the skin. Based on our own data and that reported in the literature, we hypothesize that the produced in the skin serves to suppress UVR epidermal tumor formation. In this review we will first discuss the evidence supporting the conclusion that the receptor (VDR), with or without its ligand 1,25-dihydroxyvitamin D, limits the propensity for cancer formation following UVR. We will then explore three potential mechanisms for this protection: inhibition of proliferation and stimulation of differentiation, immune regulation, and stimulation of DNA damage repair (DDR).

Photochem Photobiol Sci. 2012 Nov 19;11(12):1837-47. doi: 10.1039/c2pp25202c.

1α,25 Dihydroxyvitamin D(3) enhances cellular defences against UV-induced oxidative and other forms of DNA damage in skin.

Gordon-Thomson C, Gupta R, Tongkao-On W, Ryan A, Halliday GM, Mason RS.
Source
Department of Physiology, The Bosch Institute, The University of Sydney, NSW 2006, Australia. rebeccam at physiol.usyd.edu.au.
Abstract
DNA damage induced by ultraviolet radiation is the key initiator for skin carcinogenesis since mutations may arise from the photoproducts and it also contributes to photoimmune suppression. The active vitamin D hormone, 1α,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) reduces thymine dimers, the major photoproduct found in human skin after UV exposure, and suppresses the accumulation of nitric oxide derivatives that lead to more toxic reactive nitrogen species (RNS). We examined whether other forms of DNA damage are reduced by 1,25(OH)(2)D(3), and hypothesized that photoprotection by 1,25(OH)(2)D(3) is, in part, due to the suppression of various forms of promutagenic DNA damage, including thymine dimers, through a reduction of genotoxic RNS. Different forms of UV-induced DNA damage were investigated in irradiated skin cells treated with or without 1,25(OH)(2)D(3), or inhibitors of metabolism and inducible nitric oxide synthase. Keratinocytes were also treated with nitric oxide donors in the absence of UV light. DNA damage was assessed by comet assay incorporating site specific DNA repair endonucleases, and by immunohistochemistry using antibodies to thymine dimers or 8-Oxo-7,8-dihydro-2'-deoxyguanosine, and quantified by image analysis. Strand breaks in T4 endonuclease V, endonuclease IV and human 8-Oxoguanine DNA glycosylase digests increased more than 2-fold in UV irradiated human keratinocytes, and were reduced by 1,25(OH)(2)D(3) treatment after UV exposure, and also by low temperature, sodium azide and an inhibitor of inducible nitric oxide synthase. Conversely, nitric oxide donors induced all three types of DNA damage in the absence of UV. We present data to show that 1,25(OH)(2)D(3) protects skin cells from at least three forms of UV-induced DNA damage, and provide further evidence to support the proposal that a reduction in RNS by 1,25(OH)(2)D(3) is a likely mechanism for its photoprotective effect against oxidative and nitrative DNA damage, as well as cyclobutane pyrimidine dimers.

Maternal Vitamin D Levels and the Phenotype Among Offspring.

Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Hart PH, Kusel MM.
Source
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, 100 Roberts Road, Subiaco, West Perth, WA, 6008, Australia, awhitehouse at ichr.uwa.edu.au.
Abstract
We tested whether maternal vitamin D insufficiency during pregnancy is related to the phenotype. Serum 25(OH)-vitamin D concentrations of 929 women were measured at 18 weeks' pregnancy. The mothers of the three children with a clinical diagnosis of spectrum had 25(OH)-vitamin D concentrations above the population mean. The offspring of 406 women completed the -Spectrum Quotient in early adulthood. Maternal 25(OH)-vitamin D concentrations were unrelated to offspring scores on the majority of scales. However, offspring of mothers with low 25(OH)-vitamin D concentrations (<49 nmol/L) were at increased risk for 'high' scores (≥2SD above mean) on the Attention Switching subscale (odds ratio: 5.46, 95 % confidence interval: 1.29, 23.05). The involvement of maternal vitamin D during pregnancy in requires continued investigation.

Am J Clin Nutr. 2011 Oct;94(4):1020-5. doi: 10.3945/ajcn.111.018168. Epub 2011 Aug 10.

Vitamin D deficiency and age at menarche: a prospective study.

Villamor E, Marin C, Mora-Plazas M, Baylin A.
Source
Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA. villamor at umich.edu
Abstract
BACKGROUND:
Early menarche is a risk factor for cardiometabolic disease and cancer. Latitude, which influences sun exposure, is inversely related to age at menarche. This association might be related to vitamin D, but to our knowledge it has not been investigated in prospective epidemiologic studies.
OBJECTIVE:
We studied the association between vitamin D status and the occurrence of menarche in a prospective study in girls from Bogota, Colombia.
DESIGN:
We measured plasma 25-hydroxyvitamin D [25(OH)D] concentrations in a random sample of 242 girls (mean ± SD age: 8.8 ± 1.6 y) and followed them for a median of 30 mo. Girls were asked periodically about the occurrence and date of menarche. Baseline 25(OH)D concentrations were categorized as <50 nmol/L (deficient), ≥50 and <75 nmol/L, or ≥75 nmol/L (sufficient). The incidence of menarche was compared between groups by using time-to-event analyses.
RESULTS:
A total of 57% of girls in the vitamin D-deficient group reached menarche during follow-up compared with 23% of girls in the vitamin D-sufficient group (P-trend = 0.0004). The estimated mean (±SE) ages at menarche in the same groups were 11.8 ± 0.2 y and 12.6 ± 0.2 y, respectively (P = 0.0009). After adjustment for baseline age and BMI-for-age z score in a Cox proportional hazards model, the probability of menarche was twice as high in vitamin D-deficient girls than in girls who were vitamin D-sufficient (HR: 2.05; 95% CI: 1.03, 4.07; P = 0.04). Similar results were obtained in girls aged ≥9 y at baseline (HR: 2.39; 95% CI: 1.14, 5.00; P = 0.02).
CONCLUSION:
Vitamin D deficiency is associated with earlier menarche.

Eur Arch Psychiatry Clin Neurosci. 2012 Jun;262(4):321-7. doi: 10.1007/s00406-011-0265-8. Epub 2011 Oct 13.

Depression is associated with low levels of 25-hydroxyvitamin D among Jordanian adults: results from a national population survey.

Jaddou HY, Batieha AM, Khader YS, Kanaan SH, El-Khateeb MS, Ajlouni KM.
Source
Department of Community Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan. jaddou at just.edu.jo
Abstract
Although low serum 25-hydroxyvitamin D (25(OH)D) and elevated serum parathyroid hormone (PTH) have been associated with depression in clinical settings, this link in community-dwelling individuals is inconclusive. The present study aimed at examining the association between serum 25(OH)D and PTH levels and the presence of depression in a national population-based household sample of 4,002 Jordanian participants aged ≥25 years. The DASS21 depression scale was used to screen for depression, and serum concentrations of 25(OH)D and PTH were measured by radioimmunoassay. Multiple logistic regression models were used to explore the association between serum 25(OH)D and PTH levels and depression. The unadjusted odds ratio (OR) decreased linearly with increasing quartiles of serum 25(OH)D (P(trend) = 0.00). The OR for having depression was significantly higher among individuals in the first and second quartiles (OR = 1.4, 1.23, respectively) than among those in the fourth quartile (P values = 0.00 and 0.03, respectively). This relationship remained significant after adjusting for age, sex, marital status, education, BMI, serum creatinine, number of chronic diseases (OR = 1.39 and 1.21 and P values = 0.00 and 0.05, respectively) and after further adjustment for exercise, altitude, and smoking (OR = 1.48 and 1.24, respectively, and P values = 0.00 and 0.03, respectively). No significant association was found between serum PTH levels and depression. The decrease in risk of depression among participants started to be significant with serum 25(OH) D levels higher than 42.3 ng/ml (lower limit of the range of the third quartile). This value may help pinpoint the desirable level of serum 25(OH)D to be attained to help aid the prevention and treatment of depression.

J Sports Sci. 2012 Oct 22. [Epub ahead of print]

Assessment of vitamin D concentration in non-supplemented professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function.

Close GL, Russell J, Cobley JN, Owens DJ, Wilson G, Gregson W, Fraser WD, Morton JP.
Source
a Muscle Metabolism and Physiology Research group, Research Institute for Sport and Exercise Sciences , Liverpool John Moores University , Liverpool , UK.
Abstract
Abstract The current study implemented a two-part design to (1) assess the vitamin D concentration of a large cohort of non-vitamin D supplemented UK-based athletes and 30 age-matched healthy non-athletes and (2) to examine the effects of 5000 IU · day(-1) vitamin D(3) supplementation for 8-weeks on musculoskeletal performance in a placebo controlled trial. Vitamin D concentration was determined as severely deficient if serum 25(OH)D < 12.5 nmol · l(-1), deficient 12.5-30 nmol · l(-1) and inadequate 30-50 nmol · l(-1). We demonstrate that 62% of the athletes (38/61) and 73% of the controls (22/30) exhibited serum total 25(OH)D < 50 nmol · l(-1). Additionally, vitamin D supplementation increased serum total 25(OH)D from baseline (mean ± SD = 29 ± 25 to 103 ± 25 nmol · l(-1), P = 0.0028), whereas the placebo showed no significant change (53 ± 29 to 74 ± 24 nmol · l(-1), P = 0.12). There was a significant increase in 10 m sprint times (P = 0.008) and vertical-jump (P = 0.008) in the vitamin D group whereas the placebo showed no change (P = 0.587 and P = 0.204 respectively). The current data supports previous findings that athletes living at Northerly latitudes (UK = 53° N) exhibit inadequate vitamin D concentrations (<50 nmol · l(-1)). Additionally the data suggests that inadequate vitamin D concentration is detrimental to musculoskeletal performance in athletes. Future studies using larger athletic groups are now warranted.

Aging Dis. 2012 Aug;3(4):313-29. Epub 2012 Jun 6.

The problems of insufficiency in older people.

Boucher BJ.
Source
Queen Mary University of London, Centre for Diabetes, Blizard Institute, London, E12AT, UK.
Abstract
This report reviews evidence on disorders related to inadequate repletion in older people. is as essential for bone health in adults as in children, preventing osteomalacia and muscle weakness and protecting against falls and low-impact fractures. is provided by skin synthesis by UVB-irradiation from summer sunshine and to a small extent by absorption from food. However, these processes become less efficient with age. Loss of mobility or residential care restricts solar exposure. Reduced appetite and financial problems often add to these problems. Thus, hypovitaminosis D is common world-wide, but is more common and more severe in older people. Non-classical effects of , depending on serum circulating 25-hydroxyvitamin D concentrations, are present in most non-bony tissues; disorders associated with hypovitaminosis D include increased risks of sepsis [bacterial, mycobacterial and viral], cardiovascular and metabolic disorders [e.g. hyperlipidemia, type 2 diabetes mellitus, acute vascular events, dementia, stroke and heart failure]. Many cancer risks are associated with inadequacy, though causality is accepted only for colo-rectal cancer. Maintenance of repletion in healthy older people requires intakes of ≥800IU/day [20μg], as advised by the Institute of Medicine [IOM], but achieving such intakes usually requires supplementation. Excessive intakes are dangerous, especially in undiagnosed primary hyperparathyroidism or sarcoidosis, but the IOM finds doses <4000 IU/day are safe. Many experts suggest that ≥1000-2000 IU [25-50μg] of daily is necessary for older people, especially when independence is lost, or hypovitaminosis D could add to the clinical problem[s]. Much higher doses than these are needed for treatment of established deficiency or insufficiency.

Int Arch Allergy Immunol. 2012;157(2):168-75. doi: 10.1159/000323941. Epub 2011 Oct 6.

as a of in .

Bener A, Ehlayel MS, Tulic MK, Hamid Q.
Source
Department of Medical Statistics and Epidemiology, Hamad Medical Corporation, Doha, Qatar. abener at hmc.org.qa
Abstract
BACKGROUND:
Epidemiological studies suggest a link between in early life and development of in later life.
AIM:
The aim of this study was to measure serum levels in asthmatic and to compare these to healthy non-asthmatic controls.
METHODS:
Asthmatic (n = 483) and healthy control (n = 483) were recruited from the Pediatric Allergy-Immunology Clinics of Hamad General Hospital and the Primary Health Care Clinics in Qatar from October 2009 to July 2010. All were below 16 years of age and was diagnosed by a physician. Parents of all completed extensive questionnaires documenting demographics, child's feeding practice and intake. Serum (25-hydroxyvitamin ), calcium, phosphorus, alkaline phosphatase, magnesium, creatinine and parathyroid hormone assays were performed. Subjects with serum containing less than 20 ng/ml were deemed deficient.
RESULTS:
Asthmatic had significantly reduced serum levels compared to non-asthmatic (p < 0.001); 68.1% of all asthmatics were deficient. Asthmatic had significantly higher degrees of moderate (41.8 vs. 25.1%) and severe (26.3 vs. 11.0%) compared to healthy controls (p < 0.001). Positive familial history of (35.6%, p = 0.005) and (36.4%, p = 0.009) were significantly higher in asthmatic . Along with , asthmatics also had reduced phosphorus (p < 0.001) and magnesium (p = 0.001) levels but elevated serum alkaline phosphatase (p < 0.001) and IgE (p < 0.001). The majority of asthmatic had less exposure to sunlight (66.7%, p = 0.006) and less physical activity (71.3%, p < 0.001). was the strongest of in this population (OR 4.82; 95% CI 2.41-8.63, p < 0.001).
CONCLUSION:
The present study revealed that the majority of asthmatic had compared to control . was the major of in Qatari .

Ann Neurol. 2012 Aug 25. doi: 10.1002/ana.23738. [Epub ahead of print]

25-Hydroxyvitamin D and symptomatic ischemic stroke: An Original Study and Meta-Analysis.

Brøndum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M.
Source
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital; Faculty of Health and Medical Sciences, University of Copenhagen.
Abstract
OBJECTIVE:
We tested the hypothesis that low plasma concentrations of 25-hydroxyvitamin D are associated with increased risk of symptomatic ischemic stroke in the general population.
METHODS:
We measured plasma 25-hydroxyvitamin D in 10,170 individuals from the general population, the Copenhagen City Heart Study. During 21 years of follow-up, 1,256 and 164 persons developed ischemic and hemorrhagic stroke, respectively. In a meta-analysis of ischemic stroke, we included 10 studies, 58,384 participants, and 2,644 events.
RESULTS:
Stepwise decreasing plasma 25-hydroxyvitamin D concentrations were associated with stepwise increasing risk of ischemic stroke both as a function of seasonally adjusted percentile categories and as a function of clinical categories of 25-hydroxyvitamin D (p for trend ≤ 2 × 10(-3) ). In a Cox regression model comparing individuals with plasma 25-hydroxyvitamin D concentrations between the 1st and 4th percentiles to individuals with 25-hydroxyvitamin D concentrations between the 50th and 100th percentiles, multivariate adjusted hazard ratio of ischemic stroke was 1.82 (95% confidence interval, 1.41-2.34). Comparing individuals with clinical categories of severe vitamin D deficiency (<25.0nmol/l [<10.0ng/ml]) to individuals with optimal vitamin D status (≥75.0nmol/l [≥30.0ng/ml]), the multivariate adjusted hazard ratio of ischemic stroke was 1.36 (1.09-1.70). 25-Hydroxyvitamin D concentrations were not associated with risk of hemorrhagic stroke. In a meta-analysis comparing lowest versus highest quartile of 25-hydroxyvitamin D concentrations, the multivariate adjusted odds ratio of ischemic stroke was 1.54 (1.43-1.65) with a corresponding hazard ratio of 1.46 (1.35-1.58) in prospective general population studies.
INTERPRETATION:
In this large population-based prospective study, we observed stepwise increasing risk of symptomatic ischemic stroke with decreasing plasma 25-hydroxyvitamin D concentrations. This finding was substantiated in a meta-analysis. ANN NEUROL 2012.

Ageing Res Rev. 2012 Feb 17. [Epub ahead of print]

Serum 25-hydroxyvitamin D levels and overall mortality. A systematic review and meta-analysis of prospective cohort studies.

Schöttker B, Ball D, Gellert C, Brenner H.
Source
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Abstract
OBJECTIVE:
To provide a systematic review and meta-analysis of prospective, population-based cohort studies on the association of serum 25-hydroxyvitamin D (25(OH)D) and all-cause mortality.
METHODS:
Relevant studies were identified by systematically searching Medline, EMBASE and ISI Web of Knowledge. Reported hazard ratios (HRs) for 25(OH)D categories were recalculated employing comprehensive trend estimation from summarized dose-response data and pooled in a random effects model meta-analysis.
RESULTS:
Overall, 12 original studies were included in the review and meta-analysis comprising 32,142 mainly elderly study participants with measured 25(OH)D of whom 6921 died during follow-up. An inverse association between 25(OH)D levels and all-cause mortality was found in all but two studies that was statistically significant in several of the individual studies. In meta-analysis, 25(OH)D levels were significantly inversely associated with all-cause mortality with a pooled HR of 0.92 (95% confidence interval: 0.89-0.95) for a 20nmol/l increase in 25(OH)D levels.
CONCLUSION:
In this meta-analysis of prospective, population-based cohort studies, a 20nmol/l increase in 25(OH)D levels was associated with an 8% lower mortality in the general elderly population. This agrees with results from meta-analyses on randomized controlled trials that found a decrease in mortality with vitamin D(3) supplementation of a comparable magnitude.

Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):567-79. doi: 10.1097/MCO.0b013e3283594978.

Optimize dietary intake of : an epigenetic perspective.

Hossein-nezhad A, Holick MF.
Source
Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, , Skin and Bone Research Laboratory, Boston University Medical Center, Boston, Massachusetts 02118, USA.
Abstract
PURPOSE OF REVIEW:
has received global attention because of its many health benefits. Although there is general agreement about the importance of for bone health, there remains skepticism about the nonskeletal health benefits of . This review will not only focus on the deficiency pandemic and ways to treat and prevent deficiency but will also explore the epigenetic mechanisms of that could help explain many of the nonskeletal benefits of enhancing status.
RECENT FINDINGS:
The Institute of Medicine and the Endocrine Society have made new recommendations for intake to prevent deficiency. deficiency is defined as a 25-hydroxyvitamin D level below 20 ng/ml and insufficiency is defined as 21-29 ng/ml. Recent observations have suggested that can influence epigenetics which may help explain the nonskeletal health benefits that have been reported for .
SUMMARY:
There is general agreement that deficiency is a worldwide health problem. This is due in part to the lack of appreciation that sunlight is an important source of . There is no downside to increasing intake and recent observations suggesting that influences epigenetics provide a new insight for the importance of in utero in reducing risk of chronic diseases later in life.

Am J Obstet Gynecol. 2012 Nov 3. pii: S0002-9378(12)02035-2. doi: 10.1016/j.ajog.2012.10.888. [Epub ahead of print]

A randomized trial of supplementation in 2 community health center networks in South Carolina.

Wagner CL, McNeil R, Hamilton SA, Winkler J, Rodriguez Cook C, Warner G, Bivens B, Davis DJ, Smith PG, Murphy M, Shary JR, Hollis BW.
Source
Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, Charleston. Electronic address: wagnercl at musc.edu.
Abstract
OBJECTIVE:
We sought to determine whether 4000 IU/d (vs 2000 IU/d) of during is safe and improves maternal/neonatal 25-hydroxyvitamin D [25(OH)D] in a dose-dependent manner.
STUDY DESIGN:
A total of 257 pregnant women 12-16 weeks' gestation were enrolled. Randomization to 2000 vs 4000 IU/d followed 1-month run-in at 2000 IU/d. Participants were monitored for hypercalciuria, hypercalcemia, and 25(OH)D status.
RESULTS:
Maternal 25(OH)D (n = 161) increased from 22.7 ng/mL (SD 9.7) at baseline to 36.2 ng/mL (SD 15) and 37.9 ng/mL (SD 13.5) in the 2000 and 4000 IU groups, respectively. While maternal 25(OH)D change from baseline did not differ between groups, 25(OH)D monthly increase differed between groups (P < .01). No supplementation-related adverse events occurred. Mean cord blood 25(OH)D was 22.1 ± 10.3 ng/mL in 2000 IU and 27.0 ± 13.3 ng/mL in 4000 IU groups (P = .024). After controlling for race and study site, preterm birth and labor were inversely associated with predelivery and mean 25(OH)D, but not baseline 25(OH)D.
CONCLUSION:
Maternal supplementation with 2000 and 4000 IU/d during improved maternal/neonatal status. Evidence of risk reduction in infection, preterm labor, and preterm birth was suggestive, requiring additional studies powered for these endpoints.

Calcif Tissue Int. 2012 May 24. [Epub ahead of print]

and : Skeletal Effects, Nonskeletal Effects, and Birth Outcomes.

Hollis BW, Wagner CL.
Source
Department of Pediatrics, Darby Children's Research Institute, Medical University of South Carolina, 173 Ashley Ave., Room 313, Charleston, SC, 29425, USA, hollisb at musc.edu.
Abstract
The function and requirement of during for both mother and fetus have remained a mystery. This fact was highlighted by The Cochrane Review in 2000, which reported a lack of randomized controlled trials (RCTs) with respect to requirements during . Unfortunately, during the past decade only a single RCT has been performed with respect to requirements during . In this review we will discuss metabolism during as well as the consequences of deficiency on skeletal, nonskeletal, and birth outcomes using birth observational data and data from our recent RCT. New RCT data strongly support previous observational studies in that improving nutritional status will improve birth outcomes. The new RCT data indicate that 4,000 IU/day (3) during will "normalize" metabolism and improve birth outcomes including primary cesarean section and comorbidities of with no risk of side effects.

Nutrients. 2012 Mar;4(3):208-30. doi: 10.3390/nu4030208. Epub 2012 Mar 21.

and its role during in attaining optimal health of mother and fetus.

Wagner CL, Taylor SN, Dawodu A, Johnson DD, Hollis BW.
Source
Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 173 Ashley Avenue, MSC 513, Charleston, SC 29425, USA. wagnercl at musc.edu
Abstract
Despite its discovery a hundred years ago, has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to 's indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of supplementation during . An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Eur J Endocrinol. 2012 Jan;166(1):77-85. doi: 10.1530/EJE-11-0743. Epub 2011 Nov 2.

Association of hypogonadism with status: the European Male Ageing Study.

Lee DM, Tajar A, Pye SR, Boonen S, Vanderschueren D, Bouillon R, O'Neill TW, Bartfai G, Casanueva FF, Finn JD, Forti G, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Wu FC; EMAS study group.
Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK.
OBJECTIVE:
Interrelationships between hormones of the hypothalamic-pituitary-testicular (HPT) axis, hypogonadism, and seasonality remain poorly defined. We investigated whether HPT axis hormones and hypogonadism are associated with serum levels of 25-hydroxyvitamin D (25(OH)D) in men.
DESIGN AND METHODS:
Cross-sectional survey of 3369 community-dwelling men aged 40-79 years in eight European centres. Testosterone (T), oestradiol (E(2)) and dihydrotestosterone were measured by gas chromatography-mass spectrometry; LH, FSH, sex hormone binding globulin (SHBG), 25(OH)D and parathyroid hormone by immunoassay. Free T was calculated from total T, SHBG and albumin. Gonadal status was categorised as eugonadal (normal T/LH), secondary (low T, low/normal LH), primary (low T, elevated LH) and compensated (normal T, elevated LH) hypogonadism. Associations of HPT axis hormones with 25(OH)D were examined using linear regression and hypogonadism with using multinomial logistic regression.
RESULTS:
In univariate analyses, free T levels were lower (P=0.02) and E(2) and LH levels were higher (P<0.05) in men with deficiency (25(OH)D <50 nmol/l). 25(OH)D was positively associated with total and free T and negatively with E(2) and LH in age- and centre-adjusted linear regressions. After adjusting for health and lifestyle factors, no significant associations were observed between 25(OH)D and individual hormones of the HPT axis. However, deficiency was significantly associated with compensated (relative ratio (RRR)=1.52, P=0.03) and secondary hypogonadism (RRR=1.16, P=0.05). Seasonal variation was only observed for 25(OH)D (P<0.001).
CONCLUSIONS:
Secondary and compensated hypogonadism were associated with deficiency and the clinical significance of this relationship warrants further investigation.

Maturitas. 2012 Jan;71(1):83-8. doi: 10.1016/j.maturitas.2011.11.002. Epub 2011 Nov 17.

EMAS position statement: and postmenopausal health.

Pérez-López FR, Brincat M, Erel CT, Tremollieres F, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K, Vujovic S, Rozenberg S, Rees M.
Department of Obstetrics and Gynecology, Universidad de Zaragoza, Facultad de Medicina, Hospital Clínico, Domingo Miral s/n, Zaragoza 50009, Spain. faustino.perez at unizar.es
INTRODUCTION:
There is emerging evidence on the widespread tissue effects of .
AIMS:
To formulate a position statement on the role of in postmenopausal women.
MATERIALS AND METHODS:
Literature review and consensus of expert opinion.
RESULTS AND CONCLUSIONS:
Epidemiological and prospective studies have related deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30-90 ng/mL (75-225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of . Regular sunlight exposure (without sunscreens) for 15 min, 3-4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease.

Gastroenterology. 2012 Mar;142(3):482-9. doi: 10.1053/j.gastro.2011.11.040. Epub 2011 Dec 9.

Higher predicted status is associated with reduced of Crohn's disease.

Ananthakrishnan AN, Khalili H, Higuchi LM, Bao Y, Korzenik JR, Giovannucci EL, Richter JM, Fuchs CS, Chan AT.
Source
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02214, USA.
Abstract
BACKGROUND &#38; AIMS:
influences innate immunity, which is believed to be involved in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). However, data examining status in relation to of CD and UC are lacking.
METHODS:
We conducted a prospective cohort study of 72,719 women (age, 40-73 y) enrolled in the Nurses' Health Study. In 1986, women completed an assessment of diet and lifestyle, from which a 25-hydroxy [25(OH)D] prediction score was developed and validated against directly measured levels of plasma 25(OH)D. Through 2008, we confirmed reported diagnoses of incident CD or UC through medical record review. We used Cox proportional hazards modeling to examine the hazard ratio (HR) for incident CD or UC after adjusting for potential confounders.
RESULTS:
During 1,492,811 person-years of follow-up evaluation, we documented 122 incident cases of CD and 123 cases of UC. The median predicted 25(OH)D level was 22.3 ng/mL in the lowest and 32.2 ng/mL in the highest quartiles. Compared with the lowest quartile, the multivariate-adjusted HR associated with the highest quartile of was 0.54 (95% confidence interval [CI], 0.30-.99) for CD (P(trend) = .02) and 0.65 (95% CI, 0.34-1.25) for UC (P(trend) = .17). Compared with women with a predicted 25(OH)D level less than 20 ng/mL, the multivariate-adjusted HR was 0.38 (95% CI, 0.15-0.97) for CD and 0.57 (95% CI, 0.19-1.70) for UC for women with a predicted 25(OH)D level greater than 30 ng/mL. There was a significant inverse association between dietary and supplemental and UC, and a nonsignificant reduction in CD .
CONCLUSIONS:
Higher predicted plasma levels of 25(OH)D significantly reduce the for incident CD and nonsignificantly reduce the for UC in women.

Cancer Causes Control. 2012 Feb;23(2):363-70. doi: 10.1007/s10552-011-9885-6. Epub 2011 Dec 23.

Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: a population-based study.

Tretli S, Schwartz GG, Torjesen PA, Robsahm TE.
Source
The Cancer Registry of Norway, Institute of Population-based Cancer Research, Majorstuen, 0304 Oslo, Norway. steinar.tretli at kreftregisteret.no
PURPOSE:
We investigated the association between serum levels of 25-hydroxyvitamin D (25-OHD) and of death in Norwegian cancer patients.
METHODS:
The study population was 658 patients with cancers of the breast (n = 251), colon (n = 52), lung (n = 210), and lymphoma (n = 145), obtained from JANUS, a population-based serum bank in Norway. Serum samples were collected within 90 days of cancer diagnosis and were analyzed for 25-OHD. Patients were diagnosed during 1984-2004 and were followed for death throughout 2008. We used Cox regression models to assess the relationship between serum 25-OHD and of death.
RESULTS:
Three hundred and ninety-nine patients died during follow-up, of whom 343 (86%) died from cancer. Adjusted for sex, age at diagnosis, and season of blood sampling, patients with 25-OHD levels below 46 nmol/L at diagnosis experienced shorter survival. Compared to patients in the lowest quartile of serum 25-OHD, the of cancer death among patients in the highest quartile was significantly reduced (HR 0.36 95% CI 0.27, 0.51). The estimated change in of cancer death was most pronounced between the first and the second quartile. The associations between 25-OHD levels and survival were observed for all four cancers.
CONCLUSIONS:
Higher circulating serum levels of 25-OHD were positively associated with the survival for cancers of the breast, colon, lung, and lymphoma.

Neurobiol Aging. 2012 Oct;33(10):2382-9. doi: 10.1016/j.neurobiolaging.2011.12.002. Epub 2012 Jan 2.

Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function

Lee V, Rekhi E, Hoh Kam J, Jeffery G.
Source
University College London, Institute of Ophthalmology, UK.
Abstract
(3) plays a key role in immune regulation and may protect against the aging process. A focal point for age-related changes is the outer retina of the eye where there is high metabolic demand resulting in a gradual increase in extracellular deposition, inflammation, and cell loss giving rise to visual decline. Here, we demonstrate that (3) administration for only 6 weeks in aged mice significantly impacts on this aging process. Treated mice showed significant reductions in retinal inflammation and levels of amyloid beta (Aβ) accumulation, which is a hallmark of aging. They also had significant reductions in retinal macrophage numbers and marked shifts in their morphology. These changes were reflected in a significant improvement in visual function, revealing that (3) is a route to avoiding the pace of age-related visual decline. Excess amyloid beta deposition and inflammation are factors leading to age-related macular degeneration (AMD), the largest cause of blindness in those older than 50 years in developed countries. Recently, (3) has been linked epidemiologically to protection against age-related macular degeneration. Hence, (3) enrichment is likely to represent a beneficial route for those at .

AIDS Res Hum Retroviruses. 2012 Sep;28(9):1025-32. doi: 10.1089/AID.2011.0325. Epub 2012 Mar 23.

Hyperparathyroidism and complications associated with deficiency in HIV-infected adults in New York City, New York.

Kwan CK, Eckhardt B, Baghdadi J, Aberg JA.
Source
Bellevue Hospital Center, New York City Health and Hospital Corporation, New York, USA. ckwan at cdc.gov
Abstract
Although recent studies report a high prevalence of deficiency in HIV-infected adults similar to that in the general population, metabolic complications of deficiency may be worsened with HIV infection and remain insufficiently characterized. We conducted a retrospective cross-sectional cohort study to determine prevalence and correlates of deficiency and hyperparathyroidism among HIV-infected patients attending an urban clinic. deficiency was defined as 25(OH)- <20 ng/ml and insufficiency as 20 to <30 ng/ml, and hyperparathyroidism as parathyroid-hormone >65 pg/ml. We used the X(2) test to compare proportions and logistic regression to assess for associations. Among 463 HIV-infected patients, the prevalence of deficiency was 59%. The prevalence of hyperparathyroidism was 30% among patients with deficiency, 23% among those with insufficiency, and 12% among those with sufficient levels. deficiency was associated with increased odds of hyperparathyroidism. Severe deficiency was associated with elevated alkaline phosphatase, a marker for increased bone turnover. Although efavirenz use was associated with deficiency, and protease inhibitor use with decreased odds of deficiency, there was no statistical difference in rates of hyperparathyroidism stratified by combination antiretroviral therapy (cART) use. Given the increased of osteopenia with HIV infection and cART use, supplementation for all HIV-infected patients on cART should be prescribed in accordance with the 2011 Endocrine Society guidelines. In HIV-infected patients with severe deficiency or hyperparathyroidism, screening for osteomalacia and osteopenia may be warranted.

Pediatrics. 2012 Mar;129(3):485-93. doi: 10.1542/peds.2011-2644. Epub 2012 Feb 13.

Maternal serum levels during pregnancy and offspring neurocognitive development.

Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH.
Source
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Australia. awhitehouse at ichr.uwa.edu.au
Abstract
OBJECTIVES:
To determine the association between maternal serum 25(OH)- concentrations during a critical window of fetal neurodevelopment and behavioral, emotional, and language outcomes of offspring.
METHODS:
Serum 25(OH)- concentrations of 743 Caucasian women in Perth, Western Australia (32°S) were measured at 18 weeks pregnancy and grouped into quartiles. Offspring behavior was measured with the Child Behavior Checklist at 2, 5, 8, 10, 14, and 17 years of age (n range = 412-652). Receptive language was assessed with the Peabody Picture Vocabulary Test-Revised at ages 5 (n = 534) and 10 (n = 474) years. Raw scores were converted to standardized scores, incorporating cutoffs for clinically significant levels of difficulty.
RESULTS:
χ(2) analyses revealed no significant associations between maternal 25(OH)- serum quartiles and offspring behavioral/emotional problems at any age. In contrast, there were significant linear trends between quartiles of maternal levels and language impairment at 5 and 10 years of age. Multivariate regression analyses, incorporating a range of confounding variables, found that the of women with insufficiency (≤46 nmol/L) during pregnancy having a child with clinically significant language difficulties was increased close to twofold compared with women with levels >70 nmol/L.
CONCLUSIONS:
Maternal insufficiency during pregnancy is significantly associated with offspring language impairment. Maternal supplementation during pregnancy may reduce the of developmental language difficulties among their children.

Mil Med. 2012 Jan;177(1):70-6.

Bailey BA, Manning T, Peiris AN.
Source
Department of Family Medicine, East Tennessee State University, Johnson City, 37614, USA.
Abstract
Veterans have a profound degree of deficiency that may contribute to adverse health outcomes. Some veterans, especially African Americans at high of deficiency, may not be receiving appropriate attention. We hypothesized variations in status and monitoring across six different VAMCs and that these differences are associated with health care costs. A retrospective analysis of the medical data in the Veterans Integrated Service Network 9 (Southeastern United States) was performed, yielding a sample of 15,340 veterans. Monitoring of , levels, and medical costs and services in all categories varied greatly by site. Memphis tested levels less often despite the increased minority presence and high levels of deficiency. deficiency and lack of monitoring predicted increased inpatient health care costs at all sites, but did not fully account for site-cost variations in controlled analyses. deficiency remains a significant problem among veterans in the Southeastern United States and is closely linked to increased health care costs. We recommend protocols that recognize site differences and facilitate testing and monitoring of levels, especially in high- groups of veterans.

Paediatr Int Child Health. 2012 Feb;32(1):3-13. doi: 10.1179/1465328111Y.0000000024.

Prevention of deficiency in mothers and infants worldwide - a paradigm shift.

Dawodu A, Wagner CL.
Source
Global Health Center, Cincinnati Children's Hospital Medical Center and University of Cincinnati, 3333 Burnet Avenue, MLC 2048, Cincinnati, OH 45229, USA. adekunle.dawodu at cchmc.org
Abstract
deficiency in mothers and infants is a global health disorder despite recognition that it is preventable. Recent data support the theory that deficiency in adults and children may increase the of infections and auto-immune diseases. In most cases, deficiency is caused by sunlight deprivation and inadequate corrective intake. There is a strong mother/infant relationship that affects status both in utero and in infancy. Recognition that deficiency is a worldwide mother/infant health problem is a basis on which to modify public health strategies to reduce the burden of disease and improve maternal and child nutrition. This review provides an update on function and the global scope and implications of deficiency as it relates to pregnancy and infancy. It also addresses a combined strategy to prevent deficiency during pregnancy, lactation and infancy.

Diabetologia. 2012 Aug;55(8):2173-82. doi: 10.1007/s00125-012-2544-y. Epub 2012 Apr 15.

Circulating 25-hydroxyvitamin D concentration and the of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies.

Forouhi NG, Ye Z, Rickard AP, Khaw KT, Luben R, Langenberg C, Wareham NJ.
Source
Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Box 285, Hills Road, Cambridge, CB2 0QQ, UK. nita.forouhi at mrc-epid.cam.ac.uk
Abstract
AIMS/HYPOTHESIS:
Epidemiological evidence is suggestive, but limited, for an association between circulating 25-hydroxyvitamin D (25[OH]D) and of type 2 diabetes. We conducted a systematic review and meta-analysis that included new data from previously unpublished studies.
METHODS:
Using a nested case-cohort design in the European Prospective Investigation into Cancer (EPIC)-Norfolk study, we identified a random subcohort and incident type 2 diabetes cases occurring between baseline (1993-1997) and 2006. In the Ely prospective study we identified incident type 2 diabetes cases between 1990 and 2003. We conducted a systematic review of prospective studies on 25(OH)D and type 2 diabetes published in MEDLINE or EMBASE until 31 January 2012, and performed a random-effects meta-analysis combining available evidence with results from the EPIC-Norfolk and Ely studies.
RESULTS:
In EPIC-Norfolk, baseline 25(OH)D was lower among incident type 2 diabetes cases (mean [SD] 61.6 [22.4] nmol/l; n=621) vs non-case subcohort participants (mean 65.3 [23.9] nmol/l; n=826). There was an inverse association between baseline 25(OH)D and incident type 2 diabetes in multivariable-adjusted analyses: HR (95% CI) 0.66 (0.45, 0.97), 0.53 (0.34, 0.82), 0.50 (0.32, 0.76), p trend <0.001, comparing consecutive increasing 25(OH)D quartiles with the lowest. In Ely, 37 incident type 2 diabetes cases were identified among 777 participants. In meta-analysis, the combined RR of type 2 diabetes comparing the highest with lowest quartile of 25(OH)D was 0.59 (0.52, 0.67), with little heterogeneity (I (2) =2.7%, p=0.42) between the 11 studies included (3,612 cases and 55,713 non-cases).
CONCLUSIONS/INTERPRETATION:
These findings demonstrate an inverse association between circulating 25(OH)D and incident type 2 diabetes. However, causal inference should be addressed through adequately dosed randomised trials of supplementation or genetic Mendelian randomisation experiments.

Dement Geriatr Cogn Disord. 2012;33(5):297-305. doi: 10.1159/000339702. Epub 2012 Jul 2.

deficiency, cognitive impairment and dementia: a systematic review and meta-analysis.

Etgen T, Sander D, Bickel H, Sander K, Förstl H.
Source
Department of Psychiatry and Psychotherapy, Technische Universität München, Munich, Germany. thorleif.etgen at klinikum-traunstein.de
Abstract
BACKGROUND:
Recent preventive strategies for patients with cognitive impairment include the identification of modifiable somatic factors like deficiency.
METHODS:
A systematic literature research and meta-analysis were conducted to assess the association of cognitive impairment and deficiency.
RESULTS:
Data from cross-sectional and longitudinal studies suggest an association between cognitive impairment and deficiency. Meta-analysis of 5 cross-sectional and 2 longitudinal studies comprising 7,688 participants showed an increased of cognitive impairment in those with low compared with normal (OR 2.39, 95% CI 1.91-3.00; p < 0.0001).
CONCLUSIONS:
Methodological limitations of these studies comprise heterogeneity of study populations, different forms of cognitive assessment, the problem of reverse causality, different definitions of deficiency and inconsistent control for confounders. As the value of substitution in cognitive impairment remains doubtful, a long-time major placebo-controlled randomized trial of supplementation in participants with mild cognitive impairment (MCI) should be started.

Clin Rheumatol. 2012 Dec;31(12):1733-9. doi: 10.1007/s10067-012-2080-7. Epub 2012 Sep 2.

Association between intake and the of rheumatoid arthritis: a meta-analysis.

Song GG, Bae SC, Lee YH.
Source
Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu, Seoul, 136-705, South Korea.
Abstract
The aim of this study was to summarize published results on the association between intake and the development of rheumatoid arthritis (RA) and between serum levels and RA activity. Evidence of a relationship between intake and the development of RA and between serum levels and RA activity was studied by summarizing published results using a meta-analysis approach. Three cohort studies including 215,757 participants and 874 incident cases of RA were considered in this meta-analysis, and eight studies on the association between serum levels and RA activity involving 2,885 RA patients and 1,084 controls were included. Meta-analysis showed an association between total intake and RA incidence (relative (RR) of the highest vs. the lowest group = 0.758, 95 % confidence interval (CI) 0.577-0.937, p = 0.047), without between-study heterogeneity (I (2) = 0 %, p = 0.595). Individuals in the highest group for total intake were found to have a 24.2 % lower of developing RA than those in the lowest group. Subgroup meta-analysis also showed a significant association between supplement intake and RA incidence (RR 0.764, 95 % CI 0.628-0.930, p = 0.007), without between-study heterogeneity. All studies, except for one, found that levels are inversely associated with RA activity. One study found no correlation between levels and disease activity among 85 RA patients, but these patients had a high incidence of deficiency, which might have influenced the study outcome. Meta-analysis of 215,757 participants suggests that low intake is associated with an elevated of RA development. Furthermore, available evidence indicates that level is associated with RA activity.

Neurology. 2012 Sep 25;79(13):1397-405.

cognition, and dementia: a systematic review and meta-analysis.

Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn DJ, Raina P.
Source
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada. balion at hhsc.ca
Abstract
OBJECTIVE:
To examine the association between cognitive function and dementia with concentration in adults.
METHODS:
Five databases were searched for English-language studies up to August 2010, and included all study designs with a comparative group. Cognitive function or impairment was defined by tests of global or domain-specific cognitive performance and dementia was diagnosed according to recognized criteria. A measurement was required. Two authors independently extracted data and assessed study quality using predefined criteria. The Q statistic and I² methods were used to test for heterogeneity. We conducted meta-analyses using random effects models for the weighted mean difference (WMD) and Hedge's g.
RESULTS:
Thirty-seven studies were included; 8 contained data allowing mean Mini-Mental State Examination (MMSE) scores to be compared between participants with <50 nmol/L to those with values ≥50 nmol/L. There was significant heterogeneity among the studies that compared the WMD for MMSE but an overall positive effect for the higher group (1.2, 95% confidence interval [CI] 0.5 to 1.9; I² = 0.65; p = 0.002). The small positive effect persisted despite several sensitivity analyses. Six studies presented data comparing Alzheimer disease (AD) to controls but 2 utilized a method withdrawn from commercial use. For the remaining 4 studies the AD group had a lower concentration compared to the control group (WMD = -6.2 nmol/L, 95% CI -10.6 to -1.8) with no heterogeneity (I² < 0.01; p = 0.53).
CONCLUSION:
These results suggest that lower concentrations are associated with poorer cognitive function and a higher of AD. Further studies are required to determine the significance and potential public health benefit of this association.

Eur J Nutr. 2012 Dec 9. [Epub ahead of print]

Implications of maternal deficiency for the fetus, the neonate and the young infant.

Principi N, Bianchini S, Baggi E, Esposito S.
Source
Pediatric Clinic 1, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Commenda 9, 20122, Milan, Italy.
Abstract
BACKGROUND:
It has recently been demonstrated that (VD) deficiency during pregnancy and lactation can give rise to problems in mothers and their children.
AIM:
To discuss the implications of VD deficiency during pregnancy and the best VD supplementation to use in order to avoid risks for the mother and child.
METHODS:
PubMed was used to select all of the clinical studies published in the last 15 years concerning VD deficiency in pregnant women and its impact on the fetuses, neonates and infants, as well as the use of VD supplementation during pregnancy.
RESULTS:
Several studies have suggested that VD deficiency is associated with possible major outcomes in the preconception period, during pregnancy, perinatally and in childhood. A 25(OH)D concentration of >32 and <50-60 ng/mL seems to be associated with the lowest of disease, and the administration of 2,000 IU/day to pregnant and breastfeeding women seems to maintain adequate 25(OH)D levels. However, not all the experts agree with these conclusions because some of them do not think that VD deficiency can really cause extraskeletal manifestations and consider that the traditionally suggested 400-600 IU/day can be enough to permit an adequate bone development.
CONCLUSIONS:
Despite an increasing amount of data seems to suggest that pregnant women need a greater amount of VD than recommended in the past, further studies are needed to determine how much VD has to be given to assure a regular evolution of the pregnancy and an adequate development of the fetus and the young child.

Calcif Tissue Int. 2012 Dec 19. [Epub ahead of print]

Is High Dose Harmful?

Sanders KM, Nicholson GC, Ebeling PR.
Source
Department of Medicine, Western Health, NorthWest Academic Centre, University of Melbourne, PO Box 294, St Albans, VIC, 3021, Australia, ksanders at unimelb.edu.au.
Abstract
With the potential to minimize the of many chronic diseases and the apparent biochemical safety of ingesting doses of oral several-fold higher than the current recommended intakes, recent research has focussed on supplementing individuals with intermittent, high-dose . However, two recent randomized controlled trials (RCTs) both using annual high-dose reported an increase, rather than a decrease, in the primary outcome of fractures. This review summarises the results from studies that have used intermittent, high doses of , with particular attention to those finding evidence of adverse effects. Results from observational, population-based studies with evidence of a U- or J-shaped curve are also presented as these findings suggest an increased in those with the highest serum 25D levels. Speculative mechanisms are discussed and biochemical results from studies using high-dose are also presented. Emerging evidence from both observational studies and RCTs suggests there should be a degree of caution about recommending high serum 25D concentrations for the entire population. Furthermore, benefit of the higher doses commonly used in clinical practice on falls reduction needs to be demonstrated. The safety of loading doses of should be demonstrated before these regimens become recommended as routine clinical practice. The current dilemma of defining insufficiency and identifying safe and efficacious repletion regimens needs to be resolved.

Eur Heart J. 2012 Dec 20. [Epub ahead of print]

and of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12 000 deaths.

Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R.
Source
Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.
Abstract
AimsTo examine the independent relevance of plasma concentrations of 25-hydroxyvitamin D [25(OH)D] for vascular and non-vascular mortality.Methods and resultsWe examined associations of plasma concentrations of 25(OH)D and cause-specific mortality in a prospective study of older men living in the UK and included findings in meta-analyses of similar studies identified by a systematic search reporting on vascular and all-cause mortality. In a 13-year follow-up of 5409 men (mean baseline age 77 years), 1358 died from vascular and 1857 from non-vascular causes. Median season-adjusted baseline 25(OH)D concentration was 56 (interquartile range: 45-67) nmol/L. After adjustment for age and seasonality, higher concentrations of 25(OH)D were inversely and approximately linearly (log-log scale) associated with vascular and non-vascular mortality throughout the range 40-90 nmol/L. After additional adjustment for prior disease and cardiovascular factors, a doubling in 25(OH)D concentration was associated with 20% [95% confidence interval (CI): 9-30%] lower vascular and 23% (95% CI: 14-31%) lower non-vascular mortality. In meta-analyses of prospective studies, individuals in the top vs. bottom quarter of 25(OH)D concentrations had 21% (95% CI: 13-28%) lower vascular and 28% (95% CI: 24-32%) lower all-cause mortality.ConclusionsDespite strong inverse and apparently independent associations of 25(OH)D with vascular and non-vascular mortality, causality remains uncertain. Large-scale randomized trials, using high doses of , are required to assess the clinical relevance of these associations.

Diabetologia. 2012 Dec;55(12):3224-7. doi: 10.1007/s00125-012-2709-8. Epub 2012 Sep 7.

Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring : a nested case-control study.

Gorham ED, Garland CF, Burgi AA, Mohr SB, Zeng K, Hofflich H, Kim JJ, Ricordi C.
Source
Naval Health Research Center, 140 Sylvester Road, San Diego, CA 92106-3521, USA. Edward.Gorham at med.navy.mil
Abstract
AIMS/HYPOTHESIS:
Low serum 25-hydroxyvitamin D [25(OH)D] concentration may increase risk of insulin-requiring .
METHODS:
A nested case-control study was performed using serum collected during 2002-2008 from military service members. One thousand subjects subsequently developed insulin-requiring . A healthy control was individually matched to each case on blood-draw date (±2 days), age (±3 months), length of service (±30 days) and sex. The median elapsed time between serum collection and first diagnosis of was 1 year (range 1 month to 10 years). Statistical analysis used matched pairs and conditional logistic regression.
RESULTS:
ORs for insulin-requiring by quintile of serum 25(OH)D, from lowest to highest, were 3.5 (95% CI 2.0, 6.0), 2.5 (1.5, 4.2), 0.8 (0.4, 1.4), 1.1 (0.6, 2.8) and 1.0 (reference) (p (trend) <0.001). The quintiles (based on fifths using serum 25(OH)D concentration in the controls) of serum 25(OH)D in nmol/l, were <43 (median 28), 43-59 (median 52), 60-77 (median 70), 78-99 (median 88) and ≥100 (median 128).
CONCLUSIONS/INTERPRETATION:
Individuals with lower serum 25(OH)D concentrations had higher risk of insulin-requiring than those with higher concentrations. A 3.5-fold lower risk was associated with a serum 25(OH)D concentration ≥60 nmol/l

Am J Cardiol. 2012 Feb 1;109(3):359-63. doi: 10.1016/j.amjcard.2011.09.020. Epub 2011 Nov 8.

Vitamin D deficiency and supplementation and relation to cardiovascular health.

Vacek JL, Vanga SR, Good M, Lai SM, Lakkireddy D, Howard PA.
Source
Mid America Cardiology, Division of Cardiovascular Medicine, University of Kansas Medical Center and Hospital, Kansas City, Kansas, USA. jlvacek at mac.md
Abstract
Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.

J Clin Endocrinol Metab. 2012 Jul;97(7):2315-24. doi: 10.1210/jc.2012-1451. Epub 2012 Apr 16.

Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.

Marshall DT, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, Ambrose LH, Kindy MS, Gattoni-Celli S.
Source
Department of Radiation Oncology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Abstract
CONTEXT:
We wanted to investigate vitamin D in low-risk prostate cancer.
OBJECTIVES:
The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression.
DESIGN:
In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy.
SETTING:
All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC.
PATIENTS AND OTHER PARTICIPANTS:
All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives.
INTERVENTION:
The intervention included vitamin D(3) soft gels (4000 IU).
MAIN OUTCOME MEASURES:
Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation.
RESULTS:
No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score.
CONCLUSION:
Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.

Eur J Nutr. 2012 Aug 10. [Epub ahead of print]

Vitamin D status indicators in indigenous populations in East Africa.

Luxwolda MF, Kuipers RS, Kema IP, van der Veer E, Dijck-Brouwer DA, Muskiet FA.
Source
Laboratory Medicine, Room Y 3.181, University Medical Center Groningen (UMCG), P.O. Box 30.001, 9700 RB, Groningen, The Netherlands, mfluxwolda at hotmail.com.
Abstract
PURPOSE:
Sufficient vitamin D status may be defined as the evolutionary established circulating 25-hydroxyvitamin D [25(OH)D] matching our Paleolithic genome.
METHODS:
We studied serum 25(OH)D [defined as 25(OH)D(2) + 25(OH)D(3)] and its determinants in 5 East African ethnical groups across the life cycle: Maasai (MA) and Hadzabe (HA) with traditional life styles and low fish intakes, and people from Same (SA; intermediate fish), Sengerema (SE; high fish), and Ukerewe (UK; high fish). Samples derived from non-pregnant adults (MA, HA, SE), pregnant women (MA, SA, SE), mother-infant couples at delivery (UK), infants at delivery and their lactating mothers at 3 days (MA, SA, SE), and lactating mothers at 3 months postpartum (SA, SE). Erythrocyte docosahexaenoic acid (RBC-DHA) was determined as a proxy for fish intake.
RESULTS:
The mean ± SD 25(OH)D of non-pregnant adults and cord serum were 106.8 ± 28.4 and 79.9 ± 26.4 nmol/L, respectively. Pregnancy, delivery, ethnicity (which we used as a proxy for sunlight exposure), RBC-DHA, and age were the determinants of 25(OH)D. 25(OH)D increased slightly with age. RBC-DHA was positively related to 25(OH)D, notably 25(OH)D(2). Pregnant MA (147.7 vs. 118.3) and SE (141.9 vs. 89.0) had higher 25(OH)D than non-pregnant counterparts (MA, SE). Infant 25(OH)D at delivery in Ukerewe was about 65 % of maternal 25(OH)D.
CONCLUSIONS:
Our ancient 25(OH)D amounted to about 115 nmol/L and sunlight exposure, rather than fish intake, was the principal determinant. The fetoplacental unit was exposed to high 25(OH)D, possibly by maternal vitamin D mobilization from adipose tissue, reduced insulin sensitivity, trapping by vitamin D-binding protein, diminished deactivation, or some combination.

Br J Nutr. 2012 Nov;108(9):1557-61. doi: 10.1017/S0007114511007161. Epub 2012 Jan 23.

Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l.

Luxwolda MF, Kuipers RS, Kema IP, Janneke Dijck-Brouwer DA, Muskiet FA.
Source
Laboratory Medicine, University Medical Center Groningen (UMCG), PO Box 30.001, 9700 RB, Groningen, The Netherlands.
Abstract
Cutaneous synthesis of vitamin D by exposure to UVB is the principal source of vitamin D in the human body. Our current clothing habits and reduced time spent outdoors put us at risk of many insufficiency-related diseases that are associated with calcaemic and non-calcaemic functions of vitamin D. Populations with traditional lifestyles having lifelong, year-round exposure to tropical sunlight might provide us with information on optimal vitamin D status from an evolutionary perspective. We measured the sum of serum 25-hydroxyvitamin D2 and D3 (25(OH)D) concentrations of thirty-five pastoral Maasai (34 (sd 10) years, 43 % male) and twenty-five Hadzabe hunter-gatherers (35 (sd 12) years, 84 % male) living in Tanzania. They have skin type VI, have a moderate degree of clothing, spend the major part of the day outdoors, but avoid direct exposure to sunlight when possible. Their 25(OH)D concentrations were measured by liquid chromatography-MS/MS. The mean serum 25(OH)D concentrations of Maasai and Hadzabe were 119 (range 58-167) and 109 (range 71-171) nmol/l, respectively. These concentrations were not related to age, sex or BMI. People with traditional lifestyles, living in the cradle of mankind, have a mean circulating 25(OH)D concentration of 115 nmol/l. Whether this concentration is optimal under the conditions of the current Western lifestyle is uncertain, and should as a possible target be investigated with concomitant appreciation of other important factors in Ca homeostasis that we have changed since the agricultural revolution.

Int J Cancer. 2012 Sep 15;131(6):E1015-23. doi: 10.1002/ijc.27619. Epub 2012 May 29.

Prospective study of ultraviolet radiation exposure and risk of cancer in the United States.

Lin SW, Wheeler DC, Park Y, Cahoon EK, Hollenbeck AR, Freedman DM, Abnet CC.
Source
Cancer Prevention Fellowship Program, National Cancer Institute, Bethesda, MD 20892, USA. lins4 at mail.nih.gov
Abstract
Ecologic studies have reported that solar ultraviolet radiation (UVR) exposure is associated with cancer; however, little evidence is available from prospective studies. We aimed to assess the association between an objective measure of ambient UVR exposure and risk of total and site-specific cancer in a large, regionally diverse cohort [450,934 white, non-Hispanic subjects (50-71 years) in the prospective National Institutes of Health (NIH)-AARP Diet and Health Study] after accounting for individual-level confounding risk factors. Estimated erythemal UVR exposure from satellite Total Ozone Mapping Spectrometer (TOMS) data from NASA was linked to the US Census Bureau 2000 census tract (centroid) of baseline residence for each subject. We used Cox proportional hazards models adjusted for multiple potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quartiles of UVR exposure. Restricted cubic splines examined nonlinear relationships. Over 9 years of follow-up, UVR exposure was inversely associated with total cancer risk (N = 75,917; highest versus lowest quartile; HR = 0.97, 95% CI = 0.95-0.99; p-trend < 0.001). In site-specific cancer analyses, UVR exposure was associated with increased melanoma risk (highest versus lowest quartile; HR = 1.22, 95% CI = 1.13-1.32; p-trend < 0.001) and decreased risk of non-Hodgkin's lymphoma (HR = 0.82, 95% CI = 0.74-0.92) and colon (HR = 0.88, 95% CI = 0.82-0.96), squamous cell lung (HR = 0.86, 95% CI = 0.75-0.98), pleural (HR = 0.57, 95% CI = 0.38-0.84), prostate (HR = 0.91, 95% CI = 0.88-0.95), kidney (HR = 0.83, 95% CI = 0.73-0.94) and bladder (HR = 0.88, 95% CI = 0.81-0.96) cancers (all p-trend < 0.05). We also found nonlinear associations for some cancer sites, including the thyroid and pancreas. Our results add to mounting evidence for the influential role of UVR exposure on cancer.

Res Dev Disabil. 2012 Sep-Oct;33(5):1541-50. doi: 10.1016/j.ridd.2012.02.015. Epub 2012 Apr 21.

Vitamin D and autism: clinical review.

Kočovská E, Fernell E, Billstedt E, Minnis H, Gillberg C.
Source
Institute of Health and Wellbeing, University of Glasgow, Caledonia House, Dalnair Street, RHSC, Yorkhill, Glasgow G3 8SJ, UK. eva.kocovska at glasgow.ac.uk
Abstract
BACKGROUND:
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with multiple genetic and environmental risk factors. The interplay between genetic and environmental factors has become the subject of intensified research in the last several years. Vitamin D deficiency has recently been proposed as a possible environmental risk factor for ASD.
OBJECTIVE:
The aim of the current paper is to systematically review the research regarding the possible connection between ASD and vitamin D, and to provide a narrative review of the literature regarding the role of vitamin D in various biological processes in order to generate hypotheses for future research.
RESULTS:
Systematic data obtained by different research groups provide some, albeit very limited, support for the possible role of vitamin D deficiency in the pathogenesis of ASD. There are two main areas of involvement of vitamin D in the human body that could potentially have direct impact on the development of ASD: (1) the brain (its homeostasis, immune system and neurodevelopment) and (2) gene regulation.
CONCLUSION:
Vitamin D deficiency- -either during pregnancy or early childhood- -may be an environmental trigger for ASD in individuals genetically predisposed for the broad phenotype of autism. On the basis of the results of the present review, we argue for the recognition of this possibly important role of vitamin D in ASD, and for urgent research in the field.

J R Coll Physicians Edinb. 2012 Mar;42(1):58-63. doi: 10.4997/JRCPE.2012.114.

The evolution of human skin colouration and its relevance to health in the modern world.

Jablonski NG.
Source
Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA. ngj2 at psu.edu
Abstract
Functionally naked skin which comes in a range of colours is unique to the human species. This review summarises current evidence pertaining to the evolution of these attributes. The biggest changes in the integument occurred during the course of human evolution in equatorial Africa, under regimes of high daytime temperatures and high ultraviolet radiation (UVR). Loss of most functional body hair was accompanied by the evolution of an epidermis with a specialised stratum corneum and permanent, protective, eumelanin pigmentation. The main reason for the evolution of dark pigmentation was to protect against folate deficiency caused by elevated demands for folate in cell division, DNA repair, and melanogenesis stimulated by UVR. Dispersal out of tropical Africa created new challenges for human physiology especially because of lower and more seasonal levels of UVR and ultraviolet B (UVB) outside of the tropics. In these environments, the challenge of producing a vitamin D precursor in the skin from available UVB was met by natural selection acting on mutations capable of producing varying degrees of depigmentation. The range of pigmentation observed in modern humans today is, thus, the product of two opposing clines, one favoring photoprotection near the equator, the other favoring vitamin D photosynthesis nearer the poles. Recent migrations and changes in lifestyle in the last 500 years have brought many humans into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks, including skin cancer and vitamin D deficiency.

Philos Trans R Soc Lond B Biol Sci. 2012 Mar 19;367(1590):785-92. doi: 10.1098/rstb.2011.0308.

Human skin pigmentation, migration and disease susceptibility.

Jablonski NG, Chaplin G.
Source
Department of Anthropology, The Pennsylvania State University, University Park, PA 16802, USA. ngi2 at psu.edu
Abstract
Human skin pigmentation evolved as a compromise between the conflicting physiological demands of protection against the deleterious effects of ultraviolet radiation (UVR) and photosynthesis of UVB-dependent vitamin D(3). Living under high UVR near the equator, ancestral Homo sapiens had skin rich in protective eumelanin. Dispersals outside of the tropics were associated with positive selection for depigmentation to maximize cutaneous biosynthesis of pre-vitamin D(3) under low and highly seasonal UVB conditions. In recent centuries, migrations and high-speed transportation have brought many people into UVR regimes different from those experienced by their ancestors and, accordingly, exposed them to new disease risks. These have been increased by urbanization and changes in diet and lifestyle. Three examples-nutritional rickets, multiple sclerosis (MS) and cutaneous malignant melanoma (CMM)-are chosen to illustrate the serious health effects of mismatches between skin pigmentation and UVR. The aetiology of MS in particular provides insight into complex and contingent interactions of genetic and environmental factors necessary to trigger lethal disease states. Low UVB levels and vitamin D deficiencies produced by changes in location and lifestyle pose some of the most serious disease risks of the twenty-first century.

J Clin Endocrinol Metab. 2012 Nov 16. [Epub ahead of print]

Maternal Serum 25-Hydroxyvitamin D and Measures of Newborn and Placental Weight in a U.S. Multicenter Cohort Study.

Gernand AD, Simhan HN, Klebanoff MA, Bodnar LM.
Source
Department of Epidemiology (A.D.G.), University of Pittsburgh Graduate School of Public Health, and Departments of Epidemiology and Obstetrics and Gynecology (L.M.B.), University of Pittsburgh Graduate School of Public Health and School of Medicine, Pittsburgh, Pennsylvania 15261; Division of Maternal-Fetal Medicine (H.N.S.), Magee-Womens Hospital and Department of Obstetrics and Gynecology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Departments of Pediatrics and of Obstetrics and Gynecology (M.A.K.), Ohio State University College of Medicine and The Research Institute, Nationwide Children's Hospital, Columbus, Ohio 43210.
Abstract
Context:Inconsistent associations between maternal vitamin D status and fetal size have been published in small studies.Objective:Our objective was to examine the association between maternal 25-hydroxyvitamin D [25(OH)D] levels and measures of newborn and placental weight.Design and Setting:We measured maternal 25(OH)D in mothers from the Collaborative Perinatal Project, an observational cohort conducted in 12 U.S. medical centers from 1959 to 1965.Participants:Women delivering singleton, term, live births with 25(OH)D measured at a gestation of 26 wk or less (n = 2146).Main Outcome Measures:Birth weight, ponderal index, placental weight, the placental to fetal weight ratio, and small for gestational age were measured. Hypotheses were formulated after data collection.Results:After confounder adjustment, mothers with 25(OH)D of 37.5 nmol/liter or greater gave birth to newborns with 46 g [95% confidence interval (CI), 9-82 g] higher birth weights and 0.13 cm (0.01-0.25 cm) larger head circumferences compared with mothers with less than 37.5 nmol/liter. Birth weight and head circumference rose with increasing 25(OH)D up to 37.5 nmol/liter and then leveled off (P < 0.05). No association was observed between 25(OH)D and ponderal index, placental weight, or the placental to fetal weight ratio. Maternal 25(OH)D of 37.5 nmol/liter or greater vs. less than 37.5 nmol/liter in the first trimester was associated with half the risk of small for gestational age (adjusted odds ratio 0.5; 95% CI 0.3-0.9), but no second-trimester association was observed.Conclusions:Maternal vitamin D status is independently associated with markers of physiological and pathological growth in term infants. Adequately powered randomized controlled trials are needed to test whether maternal vitamin D supplementation may improve fetal growth.

J Clin Endocrinol Metab. 2012 Jun;97(6):1953-61. doi: 10.1210/jc.2011-3187. Epub 2012 Mar 22.

Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab).

Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, Sikaris K, Ebeling PR, Daly RM.
Source
Centre hospitalier Universitaire de Québec, Centre hospitalier de l'Université Laval, Laval University, 2705 Boulevard Laurier, Québec, Canada G1V 4G2. claudia.gagnon at crchuq.ulaval.ca
Abstract
CONTEXT:
Serum 25-hydroxyvitamin D [25(OH)D] concentration has been inversely associated with the prevalence of metabolic syndrome (MetS), but the relationship between 25(OH)D and incident MetS remains unclear.
OBJECTIVE:
We evaluated the prospective association between 25(OH)D, MetS, and its components in a large population-based cohort of adults aged 25 yr or older.
DESIGN:
We used baseline (1999-2000) and 5-yr follow-up data of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab).
PARTICIPANTS:
Of the 11,247 adults evaluated at baseline, 6,537 returned for follow-up. We studied those without MetS at baseline and with complete data (n = 4164; mean age 50 yr; 58% women; 92% Europids).
OUTCOME MEASURES:
We report the associations between baseline 25(OH)D and 5-yr MetS incidence and its components, adjusted for age, sex, ethnicity, season, latitude, smoking, family history of type 2 diabetes, physical activity, education, kidney function, waist circumference (WC), and baseline MetS components.
RESULTS:
A total of 528 incident cases (12.7%) of MetS developed over 5 yr. Compared with those in the highest quintile of 25(OH)D (≥34 ng/ml), MetS risk was significantly higher in people with 25(OH)D in the first (<18 ng/ml) and second (18-23 ng/ml) quintiles; odds ratio (95% confidence interval) = 1.41 (1.02-1.95) and 1.74 (1.28-2.37), respectively. Serum 25(OH)D was inversely associated with 5-yr WC (P < 0.001), triglycerides (P < 0.01), fasting glucose (P < 0.01), and homeostasis model assessment for insulin resistance (P < 0.001) but not with 2-h plasma glucose (P = 0.29), high-density lipoprotein cholesterol (P = 0.70), or blood pressure (P = 0.46).
CONCLUSIONS:
In Australian adults, lower 25(OH)D concentrations were associated with increased MetS risk and higher WC, serum triglyceride, fasting glucose, and insulin resistance at 5 yr. Vitamin D supplementation studies are required to establish whether the link between vitamin D deficiency and MetS is causal.

Scand J Clin Lab Invest. 2012 Nov 28. [Epub ahead of print]

Low levels of vitamin D are associated with increased mortality in patients attending a university hospital in Denmark.

Blicher TM, Jørgensen HL, Schwarz P, Wulf HC.
Source
Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen , Denmark.
Abstract
Introduction. Increased mortality in patients with low serum concentrations of S-25(OH)D has been described, though no causal relationship has been shown. The aim of this cohort study was to investigate the possible association between S-25(OH)D status and all-cause mortality in 5,147 patients attending a university hospital in Denmark from 2003-2008. Methods. Serum was analyzed for ionized calcium (S-Ca(2+)), parathyroid hormone (S-PTH) and S-25(OH)D. Kaplan-Meier curves were used to analyze the association between S-25(OH)D quartiles, S-PTH-quartiles and all-cause mortality. Cox regression analyzed associations of age, gender, concentrations of ionized calcium, S-PTH and S-25(OH)D with all-cause mortality. Results. Log rank tests for both S-25(OH)D and S-PTH quartiles showed a significant difference across the quartiles. The Cox regression analysis showed a hazard ratio (HR) for death of 1.02 (95% CI: 1.01; 1.03) for S-PTH per pmol/L increase, 1.07 (95% CI: 1.05; 1.10) for S-25(OH)D per 10 nmol/L decrease and 0.54 (95% CI: 0.24; 1.20) for S-Ca(2+) per mmol/L increase. Discussion. This study supports growing evidence, that low serum concentrations of 25(OH)D are associated with an increased all-cause mortality; however the nature of the study prevents the finding of a causal relationship. In the Cox regression analysis S-25(OH)D concentrations in the blood were inversely associated with all-cause mortality. Prospective controlled studies are needed to confirm a causal relationship between low S-25(OH)D concentrations and mortality.

Eur J Nutr. 2012 Aug 12. [Epub ahead of print]

Vitamin D metabolism, functions and needs: from science to health claims.

Battault S, Whiting SJ, Peltier SL, Sadrin S, Gerber G, Maixent JM.
Source
Équipe de Biologie Moléculaire Marine, PROTÉE, Université du Sud Toulon-Var, BP 20132, Avenue de l'Université, 83957, La Garde Cedex, France.
Abstract
BACKGROUND:
Vitamin D is a nutrient long considered as essential for skeletal health but is now attracting interest from medical and nutritional communities as knowledge emerges of its biological function and its association with decreased risk of many chronic diseases.
RESULTS:
A question emerges: How much more vitamin D do we need for these new functions of vitamin D? This review discusses vitamin D physiology and hypovitaminosis D and presents two vitamin D dietary policies: that according to regulatory authorities and that of nutrition scientists. Scientific evidence suggests that 25(OH)D serum levels should be over 75 nmol/L; otherwise, there is no beneficial effect of vitamin D on long-latency diseases. Current regulatory authority recommendations are insufficient to reach this level of adequacy. Observational and some prospective data show that vitamin D has a role in the prevention of cancer as well as immunity, diabetes and cardiovascular and muscle disorders, which supports the actions of 1α,25(OH)2D at cellular and molecular levels. The recent assessments done by the European Food Safety Authority should lead to new health claims.
CONCLUSIONS:
Vitamin D, through food fortification and supplementation, is a promising new health strategy and thus provides opportunities for food industry and nutrition researchers to work together towards determining how to achieve this potential health benefit.

Clin Chem. 2012 Dec 11. [Epub ahead of print]

Low 25-Hydroxyvitamin D and Risk of Type 2 Diabetes: A Prospective Cohort Study and Meta-analysis.

Afzal S, Bojesen SE, Nordestgaard BG.
Source
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark;
Abstract
BACKGROUND: Vitamin D deficiency has been implicated in decreased insulin secretion and increased insulin resistance, hallmarks of type 2 diabetes mellitus. We tested the hypothesis that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of type 2 diabetes in the general population.METHODS: We measured 25(OH)D in 9841 participants from the general population, of whom 810 developed type 2 diabetes during 29 years of follow-up. Analyses were adjusted for sex, age, smoking status, body mass index, income, physical activity, HDL cholesterol, and calendar month of blood draw.RESULTS: Lower 25(OH)D concentrations, by clinical categories or seasonally adjusted quartiles, were associated with higher cumulative incidence of type 2 diabetes (log-rank trend, P = 2×10(-7) and P = 4×10(-10)). Multivariable adjusted hazard ratios of type 2 diabetes were 1.22 (95% CI 0.85-1.74) for 25(OH)D <5 vs ≥20 μ g/L and 1.35 (1.09-1.66) for lowest vs highest quartile. Also, the multivariable adjusted hazard ratio of type 2 diabetes for a 50% lower concentration of 25(OH)D was 1.12 (1.03-1.21); the corresponding hazard ratio for those ≤58 years old was 1.26 (1.15-1.41). Finally, in a meta-analysis of 16 studies, the odds ratio for type 2 diabetes was 1.50 (1.33-1.70) for the bottom vs top quartile of 25(OH)D.CONCLUSIONS: We observed an association of low plasma 25(OH)D with increased risk of type 2 diabetes. This finding was substantiated in a meta-analysis.

Pediatrics. 2012 Sep;130(3):e561-7. doi: 10.1542/peds.2011-3029. Epub 2012 Aug 20.

Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia.

Camargo CA Jr, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K, Sumberzul N, Rich-Edwards JW.
Source
Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ccamargo at partners.org
Abstract
OBJECTIVE:
Observational studies suggest that serum levels of 25-hydroxyvitamin D (25[OH]D) are inversely associated with acute respiratory infections (ARIs). We hypothesized that vitamin D supplementation of children with vitamin D deficiency would lower the risk of ARIs.
METHODS:
By using cluster randomization, classrooms of 744 Mongolian schoolchildren were randomly assigned to different treatments in winter (January-March). This analysis focused on a subset of 247 children who were assigned to daily ingestion of unfortified regular milk (control; n = 104) or milk fortified with 300 IU of vitamin D(3) (n = 143). This comparison was double-blinded. The primary outcome was the number of parent-reported ARIs over the past 3 months.
RESULTS:
At baseline, the median serum 25(OH)D level was 7 ng/mL (interquartile range: 5-10 ng/mL). At the end of the trial, follow-up was 99% (n = 244), and the median 25(OH)D levels of children in the control versus vitamin D groups was significantly different (7 vs 19 ng/mL; P < .001). Compared with controls, children receiving vitamin D reported significantly fewer ARIs during the study period (mean: 0.80 vs 0.45; P = .047), with a rate ratio of 0.52 (95% confidence interval: 0.31-0.89). Adjusting for age, gender, and history of wheezing, vitamin D continued to halve the risk of ARI (rate ratio: 0.50 [95% confidence interval: 0.28-0.88]). Similar results were found among children either below or above the median 25(OH)D level at baseline (rate ratio: 0.41 vs 0.57; P(interaction) = .27).
CONCLUSIONS:
Vitamin D supplementation significantly reduced the risk of ARIs in winter among Mongolian children with vitamin D deficiency.

N Engl J Med. 2012 Jul 5;367(1):40-9. doi: 10.1056/NEJMoa1109617.

A pooled analysis of vitamin D dose requirements for fracture prevention.

Bischoff-Ferrari HA, Willett WC, Orav EJ, Lips P, Meunier PJ, Lyons RA, Flicker L, Wark J, Jackson RD, Cauley JA, Meyer HE, Pfeifer M, Sanders KM, Stähelin HB, Theiler R, Dawson-Hughes B.
Source
Center on Aging and Mobility, University of Zurich and Waid City Hospital, Zurich, Switzerland.
Erratum in
N Engl J Med. 2012 Aug 2;367(5):481. Oray, Endel J [corrected to Orav, Endel J].
Abstract
BACKGROUND:
The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent.
METHODS:
We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups.
RESULTS:
We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake.
CONCLUSIONS:
High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.).

Clin Nutr. 2012 Aug;31(4):571-3. doi: 10.1016/j.clnu.2011.12.001. Epub 2011 Dec 26.

Vitamin D and incidence of diabetes: a prospective cohort study.

González-Molero I, Rojo-Martínez G, Morcillo S, Gutiérrez-Repiso C, Rubio-Martín E, Almaraz MC, Olveira G, Soriguer F.
Source
Servicio de Endocrinología y Nutrición, Hospital Universitario Carlos Haya, Málaga, Spain. inmagonzalezmolero at hotmail.com
Abstract
BACKGROUND &#38; AIMS:
To investigate the relationship between levels of 25-hydroxyvitamin D and the incidence of type 2 diabetes in a Spanish population.
METHODS:
We undertook a population-based prospective study in a population from southern Spain. The first phase of the study (1996-1998) included 1226 individuals. Of this original cohort, 988 persons were reassessed in 2002-2004 and 961 in 2005-2007. Measurements were made of 25-hydroxyvitamin D and intact parathyroid hormone in 2002-2004 and an oral glucose tolerance test was done in three time points.
RESULTS:
The incidence of diabetes in subjects with 25-hydroxyvitamin D levels ≤ 18.5 ng/mL (percentile 25) was 12.4% vs 4.7% in subjects with levels >18.5 ng/mL. The likelihood of having diabetes during the four years of follow-up was significantly lower in the subjects with higher levels of 25-hydroxyvitamin D [OR = 0.17 (0.05-0.61)]. None of the subjects with levels higher than 30 ng/mL developed diabetes.
CONCLUSION:
In this prospective study, we found a significant inverse association between serum 25-hydroxyvitamin D levels and the risk for type 2 diabetes in a population from the south of Spain.

Am J Cardiol. 2012 Sep 15;110(6):834-9. doi: 10.1016/j.amjcard.2012.05.013. Epub 2012 Jun 2.

Serum 25-hydroxyvitamin D concentration and mortality from heart failure and cardiovascular disease, and premature mortality from all-cause in United States adults.

Liu L, Chen M, Hankins SR, Nùñez AE, Watson RA, Weinstock PJ, Newschaffer CJ, Eisen HJ; Drexel Cardiovascular Health Collaborative Education, Research, and Evaluation Group.
Source
Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA, USA. Longjian.Liu at Drexel.edu
Abstract
We aimed to examine associations between serum 25-hydroxyvitamin D (25[OH]D) concentration and mortality from heart failure (HF) and cardiovascular disease (CVD) and premature death from all causes using data from the Third National Health and Nutrition Examination Survey, which included 13,131 participants (6,130 men, 7,001 women) ≥35 years old at baseline (1988 to 1994) and followed through December 2000. Premature death was defined all-cause death at <75 years of age. Results indicated that during an average 8-year follow-up, there were 3,266 deaths (24.9%) including 101 deaths from HF, 1,451 from CVD, and 1,066 premature all-cause deaths. Among HF deaths, 37% of decedents had serum 25(OH)D levels <20 ng/ml, whereas only 26% of those with non-HF deaths had such levels (p <0.001). Multivariate-adjusted Cox model indicated that subjects with serum 25(OH)D levels <20 ng/ml had 2.06 times higher risk (95% confidence interval 1.01 to 4.25) of HF death than those with serum 25(OH)D levels ≥30 ng/ml (p <0.001). In addition, hazard ratios (95% confidence intervals) for premature death from all causes were 1.40 (1.17 to 1.68) in subjects with serum 25(OH)D levels <20 ng/ml and 1.11 (0.93 to 1.33) in those with serum 25(OH)D levels of 20 to 29 ng/ml compared to those with serum 25(OH)D levels ≥30 ng/ml (p <0.001, test for trend). In conclusion, adults with inadequate serum 25(OH)D levels have significantly higher risk of death from HF and all CVDs and all-cause premature death.

Pediatrics. 2012 Oct;130(4):e913-20. doi: 10.1542/peds.2011-3289. Epub 2012 Sep 17.

Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development.

Morales E, Guxens M, Llop S, Rodríguez-Bernal CL, Tardón A, Riaño I, Ibarluzea J, Lertxundi N, Espada M, Rodriguez A, Sunyer J; INMA Project.
Collaborators (96)
Source
Centre for Research in Environmental Epidemiology (CREAL), Parc de Recerca Biomèdica de Barcelona, Dr Aiguader 88, 08003-Barcelona, Catalonia, Spain. emorales1 at creal.cat
Abstract
OBJECTIVE:
To investigate whether circulating 25-hydroxyvitamin D(3) [25(OH)D(3)] concentration in pregnancy is associated with neuropsychological development in infants.
METHODS:
The Spanish population-based cohort study INfancia y Medio Ambiente Project recruited pregnant women during the first trimester of pregnancy between November 2003 and February 2008. Completed data on 1820 mother-infant pairs were used. Maternal plasma 25(OH)D(3) concentration was measured by high-performance liquid chromatography in pregnancy (mean 13.5 ± 2.1 weeks of gestation). Offspring mental and psychomotor scores were assessed by trained psychologists at age 14 months (range, 11-23) by using the Bayley Scales of Infant Development. β-Coefficients with 95% confidence intervals (CIs) of mental and psychomotor scores associated with continuous or categorical concentrations of maternal plasma 25(OH)D(3) were calculated by using linear regression analysis.
RESULTS:
The median plasma value of 25(OH)D(3) in pregnancy was 29.6 ng/mL (interquartile range, 21.8-37.3). A positive linear relationship was found between circulating concentrations of maternal 25(OH)D(3) concentrations in pregnancy and mental and psychomotor scores in the offspring. After adjustment for potential confounders, infants of mothers with 25(OH)D(3) concentrations in pregnancy >30 ng/mL showed higher mental score (β = 2.60; 95% CI 0.63-4.56) and higher psychomotor score (β = 2.32; 95% CI 0.36-4.28) in comparison with those of mothers with 25(OH)D(3) concentrations <20 ng/mL.
CONCLUSIONS:
Higher circulating concentration of maternal 25(OH)D(3) in pregnancy was associated with improved mental and psychomotor development in infants.

Diabetes Care. 2012 Mar;35(3):565-73. doi: 10.2337/dc11-1795. Epub 2012 Feb 8.

Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program.

Pittas AG, Nelson J, Mitri J, Hillmann W, Garganta C, Nathan DM, Hu FB, Dawson-Hughes B; Diabetes Prevention Program Research Group.
Source
Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts, USA. apittas at tuftsmedicalcenter.org
Abstract
OBJECTIVE:
To investigate the association between vitamin D status, assessed by plasma 25-hydroxyvitamin D, and risk of incident diabetes.
RESEARCH DESIGN AND METHODS:
Prospective observational study with a mean follow-up of 2.7 years in the Diabetes Prevention Program (DPP), a multicenter trial comparing different strategies for prevention of diabetes in patients with prediabetes. We assessed the association between plasma 25-hydroxyvitamin D, measured repeatedly during follow-up, and incident diabetes in the combined placebo (n = 1,022) and intensive lifestyle (n = 1,017) randomized arms of the DPP. Variables measured at multiple study time points (25-hydroxyvitamin D, BMI, and physical activity) entered the analyses as time-varying "lagged" covariates, as the mean of the previous and current visits at which diabetes status was assessed.
RESULTS:
After multivariate adjustment, including for the DPP intervention, participants in the highest tertile of 25-hydroxyvitamin D (median concentration, 30.1 ng/mL) had a hazard ratio of 0.72 (95% CI 0.56-0.90) for developing diabetes compared with participants in the lowest tertile (median concentration, 12.8 ng/mL). The association was in the same direction in placebo (0.70; 0.52-0.94) versus lifestyle arm (0.80; 0.54-1.17).
CONCLUSIONS:
Higher plasma 25-hydroxyvitamin D, assessed repeatedly, was associated with lower risk of incident diabetes in high-risk patients, after adjusting for lifestyle interventions (dietary changes, increased physical activity, and weight loss) known to decrease diabetes risk. Because of the observational nature of the study, the potential association between vitamin D and diabetes needs to be confirmed in intervention studies.

J Gerontol A Biol Sci Med Sci. 2012 Oct;67(10):1092-8. Epub 2012 Mar 27.

Association between serum 25(OH) vitamin D and the risk of cognitive decline in older women.

Slinin Y, Paudel M, Taylor BC, Ishani A, Rossom R, Yaffe K, Blackwell T, Lui LY, Hochberg M, Ensrud KE; Study of Osteoporotic Fractures Research Group.
Source
Center for Chronic Disease Outcomes Research, VA Medical Center, Minneapolis, Minnesota, USA. slini001 at umn.edu
Abstract
BACKGROUND:
Results of prospective studies examining the association between 25 hydroxyvitamin D (25[OH]D) levels and cognitive decline have been inconsistent. We tested the hypothesis that lower 25(OH)D levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline.
METHODS:
The study is a cross-sectional and longitudinal analysis of a prospective cohort of 6,257 community-dwelling elderly women followed for 4 years. Global cognitive function was measured by the Modified Mini-Mental State Examination and executive function was measured by Trail Making Test Part B (Trails B-). Cognitive impairment at baseline was defined as a score >1.5 SD below the sample mean; cognitive decline was defined as decline from baseline to follow-up >1 SD from mean change in score.
RESULTS:
Women with very low vitamin D levels had an increased odds of global cognitive impairment at baseline: odds ratio (95% confidence interval), 1.60 (1.05-2.42) for women with 25(OH)D <10 ng/mL (25 nmol/L) compared with those with 25(OH)D levels ≥30 ng/mL (75 nmol/L). Compared with women with baseline 25(OH)D level ≥30 ng/mL (75 nmol/L), women with lower levels had an increased risk of global cognitive decline: odds ratio (95% confidence interval), 1.58(1.12-2.22) for women with levels <10 ng/mL (25 nmol/L), and 1.31 (1.04-1.64) for those with levels 10-19.9 ng/mL (25-49 nmol/L). Levels of 25(OH)D were not associated with executive cognitive function.
CONCLUSIONS:
Low 25(OH)D levels among older women were associated with a higher odds of global cognitive impairment and a higher risk of global cognitive decline.

Am J Epidemiol. 2012 Nov 1. [Epub ahead of print]

A Prospective Study of Serum 25-Hydroxyvitamin D Levels and Mortality Among African Americans and Non-African Americans.

Signorello LB, Han X, Cai Q, Cohen SS, Cope EL, Zheng W, Blot WJ.
Abstract
The beneficial biologic effects attributed to vitamin D suggest a potential to influence overall mortality. Evidence addressing this hypothesis is limited, especially for African Americans who have a high prevalence of vitamin D insufficiency. The authors conducted a nested case-control study within the prospective Southern Community Cohort Study to relate baseline serum levels of 25-hydroxyvitamin D (25(OH)D) with subsequent mortality. Cases were 1,852 participants who enrolled from 2002 to 2009 and died >12 months postenrollment. Controls (n = 1,852) were matched on race, sex, age, enrollment site, and blood collection date. The odds ratios for quartile 1 (<10.18 ng/mL) versus quartile 4 (>21.64 ng/mL) levels of 25(OH)D were 1.60 (95% confidence interval (CI): 1.20, 2.14) for African Americans and 2.11 (95% CI: 1.39, 3.21) for non-African Americans. The effects were strongest for circulatory disease death, where quartile 1 versus quartile 4 odds ratios were 2.53 (95% CI: 1.44, 4.46) and 3.25 (95% CI: 1.33, 7.93) for African Americans and non-African Americans, respectively. The estimated odds of total mortality were minimized in the 25(OH)D range of 35-40 ng/mL. These findings provide support for the hypothesis that vitamin D status may have an important influence on mortality for both African Americans and non-African Americans.

Circ Cardiovasc Qual Outcomes. 2012 Nov 1;5(6):819-29. doi: 10.1161/CIRCOUTCOMES.112.967604. Epub 2012 Nov 13.

Circulating 25-hydroxy-vitamin d and risk of cardiovascular disease: a meta-analysis of prospective studies.

Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C, Eaton CB, May HT, Anderson JL, Sesso HD.
Source
Division of Preventive Medicine.
Abstract
Background- Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear. Methods and Results- We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below ≈60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D. Conclusions- This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations.

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