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Increased chance of death if enter hospital with vitamin D greater than 60 ng (u-shaped) – April 2014

Evidence for a u-shaped relationship between prehospital vitamin d status and mortality: a cohort study.

J Clin Endocrinol Metab. 2014 Apr;99(4):1461-9. doi: 10.1210/jc.2013-3481. Epub 2014 Jan 13.
Amrein K 1, Quraishi SA, Litonjua AA, Gibbons FK, Pieber TR, Camargo CA Jr, Giovannucci E, Christopher KB.
1 Division of Endocrinology and Metabolism (K.A.), Department of Internal Medicine, and Division of Endocrinology and Metabolism (T.R.P.), Department of Internal Medicine, Medical University of Graz, A-8036 Graz, Austria; Department of Anesthesia, Critical Care, and Pain Medicine (S.A.Q.), Division of Pulmonary and Critical Care Medicine (F.K.G.), Department of Medicine, and Department of Emergency Medicine (C.A.C.), Massachusetts General Hospital, Boston, Massachusetts 02114; Channing Division of Network Medicine and Pulmonary and Critical Care Division (A.A.L.), Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Departments of Nutrition and Epidemiology (E.G.), Harvard School of Public Health, and The Nathan E. Hellman Memorial Laboratory (K.B.C.), Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.

Objective: The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission.

Design: We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. Setting: The study was conducted at two Boston teaching hospitals.

Patients: A total of 24 094 adult inpatients participated in the study.

Intervention: There was no intervention.

Measurements: All patients had serum 25(OH)D measured before hospitalization.
The exposure of interest was 25(OH)D categorized as

  • less than 10 ng/mL,
  • 10-19.9 ng/mL,
  • 20-29.9 ng/mL,
  • 30-49.9 ng/mL,
  • 50-59.9 ng/mL,
  • 60-69.9 ng/mL, and
  • 70 ng/mL or greater.

The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders.

Results: After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and ≥70 ng/mL was

  • 2.01 (1.68-2.40),
  • 1.89 (1.64-2.18),
  • 1.34 (1.16-1.56),
  • 0.94 (0.69-1.26),
  • 1.52 (1.03-2.25), and
  • 1.69 (1.09-2.61),

respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL].

Limitations: A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study.

Conclusions: Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.

PMID: 24423347

References

  • 1. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012;95(1):91–100. [CrossRef] [Medline]
  • 2. Ginde AA, Scragg R, Schwartz RS, Camargo CA Jr. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older US adults. J Am Geriatr Soc. 2009;57(9):1595–1603. [CrossRef] [Medline]
  • 3. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730–1737. [CrossRef] [Medline]
  • 4. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011(7):CD007470. [Medline]
  • 5. Peterlik M. Vitamin D insufficiency and chronic diseases: hype and reality. Food Funct. 2012;3(8):784–794. [CrossRef]
  • 6. Lange N, Litonjua AA, Gibbons FK, Giovannucci E, Christopher KB. Pre-hospital vitamin D concentration, mortality, and bloodstream infection in a hospitalized patient population. Am J Med. 2013;126(7):640.e619–e627. [CrossRef]
  • 7. Lai JK, Lucas RM, Clements MS, Harrison SL, Banks E. Assessing vitamin D status: pitfalls for the unwary. Mol Nutr Food Res. 2010;54(8):1062–1071. [Medline]
  • 8. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–281. [CrossRef] [Medline]
  • 9. Heaney RP. Assessing vitamin D status. Curr Opin Clin Nutr Metab Care. 2011;14(5):440–444. [CrossRef] [Medline]
  • 10. Vieth R. Vitamin D toxicity, policy, and science. J Bone Miner Res. 2007;22(suppl 2):V64–V68. [CrossRef] [Medline]
  • 11. Heaney RP, Holick MF. Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res. 2011;26(3):455–457. [CrossRef] [Medline]
  • 12. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(7):1911–1930. [Abstract] [Medline]
  • 13. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2011.
  • 14. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752–757; quiz 757–758. [CrossRef] [Medline]
  • 15. Melamed ML, Michos ED, Post W, Astor B. 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168(15):1629–1637. [CrossRef] [Medline]
  • 16. Michaelsson K, Baron JA, Snellman G, et al. Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr. 2010;92(4):841–848. [CrossRef] [Medline]
  • 17. Jia X, Aucott LS, McNeill G. Nutritional status and subsequent all-cause mortality in men and women aged 75 years or over living in the community. Br J Nutr. 2007;98(3):593–599. [CrossRef] [Medline]
  • 18. Visser M, Deeg DJ, Puts MT, Seidell JC, Lips P. Low serum concentrations of 25-hydroxyvitamin D in older persons and the risk of nursing home admission. Am J Clin Nutr. 2006;84(3):616–622; quiz 671–672. [Medline]
  • 19. Ginde AA, Liu MC, Camargo CA Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch Intern Med. 2009;169(6):626–632. [CrossRef] [Medline]
  • 20. 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. 2013;52(3):1115–1125. [CrossRef] [Medline]
  • 21. Bolland MJ, Grey A, Davidson JS, Cundy T, Reid IR. Should measurement of vitamin D and treatment of vitamin D insufficiency be routine in New Zealand? NZ Med J. 2012;125(1349):83–91. [Medline]
  • 22. Binkley N, Novotny R, Krueger D, et al. Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab. 2007;92(6):2130–2135. [Abstract] [Medline]
  • 23. Bilinski K, Boyages S. The rise and rise of vitamin D testing. BMJ. 2012;345:e4743. [CrossRef] [Medline]
  • 24. Nutrition Business Journal. 2012 Global supplement, nutrition industry report, 2012. http://newhope360.com/nutrition-business-journal. Accessed March 2, 2013.
  • 25. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007;85(1):6–18. [Medline]
  • 26. Haines ST, Park SK. Vitamin D supplementation: what's known, what to do, and what's needed. Pharmacotherapy. 2012;32(4):354–382. [CrossRef] [Medline]
  • 27. Zager S, Mendu ML, Chang D, et al. Neighborhood poverty rate and mortality in patients receiving critical care in the academic medical center setting. Chest. 2011;139(6):1368–1379. [CrossRef] [Medline]
  • 28. Rapoport J, Gehlbach S, Lemeshow S, Teres D. Resource utilization among intensive care patients. Managed care vs traditional insurance. Arch Intern Med. 1992;152(11):2207–2212. [CrossRef] [Medline]
  • 29. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. [CrossRef] [Medline]
  • 30. Quan H, Sundararajan V, Halfon P, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Med Care. 2005;43(11):1130–1139. [CrossRef] [Medline]
  • 31. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–682. [CrossRef] [Medline]
  • 32. Braun A, Chang D, Mahadevappa K, et al. Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill. Crit Care Med. 2011;39(4):671–677. [CrossRef] [Medline]
  • 33. Braun AB, Gibbons FK, Litonjua AA, Giovannucci E, Christopher KB. Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med. 2012;40(1):63–72. [CrossRef] [Medline]
  • 34. Cowper DC, Kubal JD, Maynard C, Hynes DM. A primer and comparative review of major US mortality databases. Ann Epidemiol. 2002;12(7):462–468. [CrossRef] [Medline]
  • 35. Sohn MW, Arnold N, Maynard C, Hynes DM. Accuracy and completeness of mortality data in the Department of Veterans Affairs. Popul Health Metr. 2006;4:2. [CrossRef] [Medline]
  • 36. Schisterman EF, Whitcomb BW. Use of the Social Security Administration Death Master File for ascertainment of mortality status. Popul Health Metr. 2004;2(1):2. [CrossRef] [Medline]
  • 37. Newman TB, Brown AN. Use of commercial record linkage software and vital statistics to identify patient deaths. J Am Med Inform Assoc. 1997;4(3):233–237. [CrossRef] [Medline]
  • 38. Cleveland W. Robust locally weighted regression and smoothing scatterplots. J Am Stat Assoc. 1979;74(368):829–836. [CrossRef]
  • 39. Cleveland W, Devlin S. Locally weighted regression: an approach to regression analysis by local fitting. J Am Stat Assoc. 1988;83(403):596–610. [CrossRef]
  • 40. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–481. [CrossRef]
  • 41. Lowe H, Cusano NE, Binkley N, Blaner WS, Bilezikian JP. Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. J Clin Endocrinol Metab. 2011;96(2):291–295. [Abstract] [Medline]
  • 42. Sempos CT, Durazo-Arvizu RA, Dawson-Hughes B, et al. Is there a reverse J-shaped association between 25-hydroxyvitamin D and all-cause mortality? Results from the US Nationally Representative NHANES. J Clin Endocrinol Metab. 2013;98(7):3001–3009. [Abstract] [Medline]
  • 43. Vieth R. The mechanisms of vitamin D toxicity. Bone Miner. 1990;11(3):267–272. [CrossRef] [Medline]
  • 44. Smith H, Anderson F, Raphael H, Maslin P, Crozier S, Cooper C. Effect of annual intramuscular vitamin D on fracture risk in elderly men and women—a population-based, randomized, double-blind, placebo-controlled trial. Rheumatology (Oxford). 2007;46(12):1852–1857. [CrossRef] [Medline]
  • 45. Sanders KM, Stuart AL, Williamson EJ, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303(18):1815–1822. [CrossRef] [Medline]
  • 46. Ilahi M, Armas LA, Heaney RP. Pharmacokinetics of a single, large dose of cholecalciferol. Am J Clin Nutr. 2008;87(3):688–691. [Medline]
  • 47. Amer M, Qayyum R. Relation between serum 25-hydroxyvitamin D and C-reactive protein in asymptomatic adults (from the continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol. 2012;109(2):226–230. [CrossRef] [Medline]
  • 48. Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G. Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation. 2005;112(17):2627–2633. [CrossRef] [Medline]
  • 49. Larsson TE, Olauson H, Hagstrom E, et al. Conjoint effects of serum calcium and phosphate on risk of total, cardiovascular, and noncardiovascular mortality in the community. Arterioscler Thromb Vasc Biol. 2010;30(2):333–339. [CrossRef] [Medline]
  • 50. Premaor MO, Alves GV, Crossetti LB, Furlanetto TW. Hyperparathyroidism secondary to hypovitaminosis D in hypoalbuminemic is less intense than in normoalbuminemic patients: a prevalence study in medical inpatients in southern Brazil. Endocrine. 2004;24(1):47–53. [CrossRef] [Medline]
  • 51. Bikle DD, Gee E, Halloran B, Kowalski MA, Ryzen E, Haddad JG. Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. J Clin Endocrinol Metab. 1986;63(4):954–959. [Abstract] [Medline]
  • 52. Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E. Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control. 2004;15(3):255–265. [CrossRef] [Medline]
  • 53. Krishnan A, Ochola J, Mundy J, et al. Acute fluid shifts influence the assessment of serum vitamin D status in critically ill patients. Crit Care. 2010;14(6):R216. [CrossRef] [Medline]
  • 54. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–58. [Abstract] [Medline]
  • 55. Mata-Granados JM, Vargas-Vasserot J, Ferreiro-Vera C, Luque de Castro MD, Pavon RG, Quesada Gomez JM. Evaluation of vitamin D endocrine system (VDES) status and response to treatment of patients in intensive care units (ICUs) using an on-line SPE-LC-MS/MS method. J Steroid Biochem Mol Biol. 2010;121(1–2):452–455. [CrossRef] [Medline]
  • 56. Esper AM, Moss M, Lewis CA, Nisbet R, Mannino DM, Martin GS. The role of infection and comorbidity: factors that influence disparities in sepsis. Crit Care Med. 2006;34(10):2576–2582. [CrossRef] [Medline]
  • 57. Clinical utility of vitamin d testing: an evidence-based analysis. Ont Health Technol Assess Ser. 2010;10(2):1–93.

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Summary by VitaminDWiki

ng/mL Mortality Risk
< 102.01
10-19.91.89
20-29.91.34
30-49.91.00
50-59.90.94
60-69.91.52
>701.69

25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study. (May 2014)

J Intern Med. 2014 May 31. doi: 10.1111/joim.12273. [Epub ahead of print]
Granic A1, Aspray T, Hill T, Davies K, Collerton J, Ruiz CM, von Zglinicki T, Kirkwood TB, Mathers JC, Jagger C.

OBJECTIVE:
To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years.
DESIGN, SETTING AND SUBJECTS:
Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (non-users of vitamin D-containing supplements and medication) cohorts.
RESULTS:
For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles (SQ2+SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02), and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol/L) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates.
CONCLUSION:
Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.
This article is protected by copyright. All rights reserved.

PMID: 24889485
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