A Predictive Equation to Guide Vitamin D Replacement Dose in Patients

Background: Vitamin D is essential for bone health and probably the health of most nonskeletal tissues. Vitamin D deficiency is widespread, and recommended doses are usually inadequate to maintain healthy levels. We conducted a retrospective observational study to determine whether the recommended doses of vitamin D are adequate to correct deficiency and maintain normal levels in a population seeking health care. We also sought to develop a predictive equation for replacement doses of vitamin D. Methods: We reviewed the response to vitamin D supplementation in 1327 patients and 3885 episodes of vitamin D replacement and attempted to discern factors affecting the response to vitamin D replacement by conducting multiple regression analyses. Results: For the whole population, average daily dose resulting in any increase in serum 25-hydroxyvitamin D level was 4707 IU/day; corresponding values for ambulatory and nursing home patients were 4229 and 6103 IU/day, respectively. Significant factors affecting the change in serum concentrations of 25-hydroxyvitamin D, in addition to the dose administered, are (1) starting serum concentration of 25-hydroxyvitamin D, (2) body mass index (BMI), (3) age, and (f) serum albumin concentration. The following equation predicts the dose of vitamin D needed (in international units per day) to affect a given change in serum concentrations of 25-hydroxyvitamin D: Dose = [(8.52 − Desired change in serum 25-hydroxyvitamin D level) + (0.074 × Age) – (0.20 × BMI) + (1.74 × Albumin concentration) – (0.62 × Starting serum 25-hydroxyvitamin D concentration)]/(−0.002). Analysis of the dose responses among 3 racial groups—white, black, and others—did not reveal clinically meaningful differences between the races. The main limitation of the study is its retrospective observational nature; however, that is also its strength in that we assessed the circumstances seen in usual health care setting. Conclusions: The recommended daily allowance for vitamin D is grossly inadequate for correcting low serum concentrations of 25-hydroxyvitamin D in many adult patients. About 5000 IU vitamin D3/day is usually needed to correct deficiency, and the maintenance dose should be ≥2000 IU/day. The required dose may be calculated from the predictive equations specific for ambulatory and nursing home patients.

[1]  Christine L. Taylor,et al.  Dietary Reference Intakes for Calcium and Vitamin D , 2016, Pediatric Clinical Practice Guidelines & Policies.

[2]  I. Reid,et al.  The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. , 2014, The lancet. Diabetes & endocrinology.

[3]  P. Norman,et al.  Vitamin D and cardiovascular disease. , 2014, Circulation research.

[4]  Ishir Bhan,et al.  Vitamin D-binding protein and vitamin D status of black Americans and white Americans. , 2013, The New England journal of medicine.

[5]  J. Eisman.  When is a U-curve actually a J-curve? Is it really too much of a good thing? , 2013, The Journal of clinical endocrinology and metabolism.

[6]  M. Porteous,et al.  Vitamin D insufficiency in osteoporotic hip fracture patients: rapid substitution therapy with high dose oral cholecalciferol (vitamin D3). , 2013, Acta orthopaedica Belgica.

[7]  M. Holick,et al.  Vitamin D for health: a global perspective. , 2013, Mayo Clinic proceedings.

[8]  D. McMahon,et al.  Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis. , 2013, The Journal of clinical endocrinology and metabolism.

[9]  R. Collins,et al.  Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. , 2013, European heart journal.

[10]  R. Heaney,et al.  All-source basal vitamin D inputs are greater than previously thought and cutaneous inputs are smaller. , 2013, The Journal of nutrition.

[11]  S. Bojesen,et al.  Low plasma 25-hydroxyvitamin D and risk of tobacco-related cancer. , 2013, Clinical chemistry.

[12]  N. Cook.  Vitamin D and cancer: can we believe the evidence from observational studies? , 2013, Clinical chemistry.

[13]  W. März,et al.  Vitamin D and mortality: a Mendelian randomization study. , 2013, Clinical chemistry.

[14]  M. Hoshen,et al.  Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association. , 2013, The Journal of clinical endocrinology and metabolism.

[15]  C. Cooper,et al.  Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) , 2013, Current medical research and opinion.

[16]  B. Caballero,et al.  Modern nutrition in health and disease: Eleventh edition , 2012 .

[17]  Lynette M. Smith,et al.  Dose Response to Vitamin D Supplementation in Postmenopausal Women , 2012, Annals of Internal Medicine.

[18]  W. Willett,et al.  A pooled analysis of vitamin D dose requirements for fracture prevention. , 2012, The New England journal of medicine.

[19]  R. Heaney,et al.  Volumetric Dilution, Rather Than Sequestration Best Explains the Low Vitamin D Status of Obesity , 2012, Obesity.

[20]  JoAnn E Manson,et al.  The nonskeletal effects of vitamin D: an Endocrine Society scientific statement. , 2012, Endocrine reviews.

[21]  C. Gordon,et al.  Guidelines for preventing and treating vitamin D deficiency and insufficiency revisited. , 2012, The Journal of clinical endocrinology and metabolism.

[22]  Lynette M. Smith,et al.  Dose Response to Vitamin D Supplementation in Postmenopausal Women , 2012, Annals of Internal Medicine.

[23]  M. Holick,et al.  Vitamin D supplementation: guidelines and evidence for subclinical deficiency , 2012, Current opinion in gastroenterology.

[24]  S. Wimalawansa.  Vitamin D: an essential component for skeletal health , 2011, Annals of the New York Academy of Sciences.

[25]  W. Grant.  An estimate of the global reduction in mortality rates through doubling vitamin D levels , 2011, European Journal of Clinical Nutrition.

[26]  R. Vieth.  Why the minimum desirable serum 25-hydroxyvitamin D level should be 75 nmol/L (30 ng/ml). , 2011, Best practice & research. Clinical endocrinology & metabolism.

[27]  C. Gordon,et al.  Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. , 2011, The Journal of clinical endocrinology and metabolism.

[28]  T. Greulich,et al.  The role of vitamin D in pulmonary disease: COPD, asthma, infection, and cancer , 2011, Respiratory research.

[29]  M. Herrmann,et al.  Supplementation with vitamin D and calcium in long-term care residents. , 2011, Journal of the American Medical Directors Association.

[30]  R. Heaney,et al.  Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. , 2011, Anticancer research.

[31]  M. Tinetti,et al.  Summary of the Updated American Geriatrics Society/British Geriatrics Society Clinical Practice Guideline for Prevention of Falls in Older Persons , 2011, Journal of the American Geriatrics Society.

[32]  M. Holick,et al.  A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness. , 2010, The Journal of clinical endocrinology and metabolism.

[33]  S. Genuis,et al.  Vitamin D supplementation in a nursing home population. , 2010, Molecular nutrition & food research.

[34]  K. Dodd,et al.  Estimation of total usual calcium and vitamin D intakes in the United States. , 2010, The Journal of nutrition.

[35]  J. Adams,et al.  Update in vitamin D. , 2010, The Journal of clinical endocrinology and metabolism.

[36]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2008. , 2010, JAMA.

[37]  J. Reichrath,et al.  Cutaneous vitamin D synthesis versus skin cancer development , 2009, Dermato-endocrinology.

[38]  K. Schechtman,et al.  1,25(OH)2 Vitamin D Inhibits Foam Cell Formation and Suppresses Macrophage Cholesterol Uptake in Patients With Type 2 Diabetes Mellitus , 2009, Circulation.

[39]  L. Ferrucci,et al.  Low serum 25-hydroxyvitamin D concentrations are associated with greater all-cause mortality in older community-dwelling women. , 2009, Nutrition research.

[40]  C. Camargo,et al.  Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. , 2009, Archives of internal medicine.

[41]  J. Moan,et al.  Estimated benefit of increased vitamin D status in reducing the economic burden of disease in western Europe. , 2009, Progress in biophysics and molecular biology.

[42]  W. Grant.  A critical review of Vitamin D and cancer: A report of the IARC Working Group on vitamin D , 2009, Dermato-endocrinology.

[43]  B. Boehm,et al.  Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. , 2008, Archives of internal medicine.

[44]  E. Rimm,et al.  25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. , 2008, Archives of internal medicine.

[45]  K. Zhu,et al.  Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. , 2008, Archives of internal medicine.

[46]  Andrei Javier,et al.  Vitamin D deficiency. , 2007, The New England journal of medicine.

[47]  G. Baroncelli,et al.  Vitamin D deficiency. , 2007, The New England journal of medicine.

[48]  B. Graubard,et al.  Prospective study of serum vitamin D and cancer mortality in the United States. , 2007, Journal of the National Cancer Institute.

[49]  Sara Gandini,et al.  Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. , 2007, Archives of internal medicine.

[50]  Bess Dawson-Hughes,et al.  The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. , 2007, The Journal of clinical endocrinology and metabolism.

[51]  E. Giovannucci,et al.  Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. , 2007, American journal of preventive medicine.

[52]  E. Giovannucci,et al.  Vitamin D and prevention of breast cancer: Pooled analysis , 2007, The Journal of Steroid Biochemistry and Molecular Biology.

[53]  W. Willett,et al.  The urgent need to recommend an intake of vitamin D that is effective. , 2007, The American journal of clinical nutrition.

[54]  Jennifer Lin,et al.  Intakes of calcium and vitamin D and breast cancer risk in women. , 2006, Archives of internal medicine.

[55]  Yan Liu,et al.  Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. , 2006, Journal of the National Cancer Institute.

[56]  Barbara A Gilchrest,et al.  The vitamin D questions: how much do you need and how should you get it? , 2006, Journal of the American Academy of Dermatology.

[57]  J. Manson,et al.  Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. , 2005, Diabetes care.

[58]  H. Jha,et al.  Novel tempeh (fermented soyabean) isoflavones inhibit in vivo angiogenesis in the chicken chorioallantoic membrane assay , 2005, British Journal of Nutrition.

[59]  B. Hollis.  Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. , 2005, The Journal of nutrition.

[60]  M. Gross.  Vitamin D and calcium in the prevention of prostate and colon cancer: new approaches for the identification of needs. , 2005, The Journal of nutrition.

[61]  M. Holick.  Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. , 2004, The American journal of clinical nutrition.

[62]  A. Sadovnick,et al.  Vitamin D intake and incidence of multiple sclerosis , 2004, Neurology.

[63]  H. Bischoff-Ferrari,et al.  Association between serum concentrations of 25-hydroxyvitamin D3 and periodontal disease in the US population. , 2004, The American journal of clinical nutrition.

[64]  K. Flegal,et al.  Prevalence and trends in obesity among US adults, 1999-2000. , 2002, JAMA.

[65]  G. Fitzmaurice,et al.  A conundrum in the analysis of change. , 2001, Nutrition.

[66]  M. Holick,et al.  Sunlight “D”ilemma: risk of skin cancer or bone disease and muscle weakness , 2001, The Lancet.

[67]  M. Seikaly,et al.  Nutritional rickets still afflict children in north Texas. , 2000, Texas medicine.

[68]  R. Garg,et al.  Severe myopathy associated with vitamin D deficiency in western New York. , 2000, Archives of internal medicine.

[69]  R. Recker,et al.  Vitamin D treatment in myelodysplastic syndromes , 1998, British journal of haematology.

[70]  D. Felson,et al.  Relation of Dietary Intake and Serum Levels of Vitamin D to Progression of Osteoarthritis of the Knee among Participants in the Framingham Study , 1996, Annals of Internal Medicine.

[71]  N. Callaghan,et al.  A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia. , 1991, The Quarterly journal of medicine.

[72]  M. Holick,et al.  Sunscreens suppress cutaneous vitamin D3 synthesis. , 1987, The Journal of clinical endocrinology and metabolism.

[73]  J. Haddad,et al.  Assessment of the free fraction of 25-hydroxyvitamin D in serum and its regulation by albumin and the vitamin D-binding protein. , 1986, The Journal of clinical endocrinology and metabolism.

[74]  T. Oppé,et al.  Vitamin D deficiency. , 1979, British medical journal.

[75]  H. Pols,et al.  Vitamin D , 1928, Calcified Tissue International.

[76]  Gurmukh Singh.  Prevalence and implications of vitamin D deficiency in applicants for insurance. , 2014, Journal of insurance medicine.

[77]  K. Forrest,et al.  Prevalence and correlates of vitamin D deficiency in US adults. , 2011, Nutrition research.

[78]  Christine L. Taylor,et al.  Committee to Review Dietary Reference Intakes for Vitamin D and Calcium , 2011 .

[79]  A. MacLullich,et al.  a systematic review and meta-analysis , 2011 .

[80]  Journal of Translational Medicine BioMed Central Review Surgical inflammation: a pathophysiological rainbow , 2009 .

[81]  N. Goldenberg,et al.  Low serum 25 (OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. , 2009, Translational research : the journal of laboratory and clinical medicine.

[82]  Graham R D Jones,et al.  Reference intervals. , 2008, The Clinical biochemist. Reviews.

[83]  S. Page.  Dietary Supplement Fact Sheet Vitamin D , 2005 .

[84]  M. Holick,et al.  Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. , 2003, The American journal of clinical nutrition.