2.  Hormone: › from Greek “impetus” chemical released by a cell that affect cells in other parts › is a chemical released by a cell in one part of an organism, that sends out messages that affect cells in other parts of the organism  Vitamin: external source, food › essential organic micronutrient that can only be obtained from an external source, food

4.  25(OH)D or calcidiol › Inactive form › 2-3 week ½-life › Major circulating form of Vitamin D › best indicator of status  1,25(OH) 2 D or calcitriol › Active form › 4 hour ½-life › Regulated by serum levels of PTH, Ca, PO4 › Levels normal or elevated in 2’hyperPTH › Does not reflect Vitamin D stores

5. Vitamin D status by blood levels of 25(OH)D Vitamin D status25(OH)D ng/mL Sufficient ≥ 30 Insufficient 20 to 29 Optimal30-60 Side effects 88 Moyad, MA. (2008). Vitamin d: a rapid review. Urol Nurs, Oct 28(5), 343-349. Potentially harmful/ intoxication >150 Holick MF. (2007). Vitamin d deficiency. NEJM, 357(3), 266–80.

6.  Adults: INSUFFICIENT/DEFICIENT:  11-50% of healthy adults  Age, season, location  Peds/Adolescents: › INSUFFICIENT: 61% › DEFICIENT: 9% Kumar, et al. (2009). Prevalence and Associations of 25-Hydroxyvitamin D Deficiency in US Children: NHANES 2001-2004 Pediatrics, 124(3), 362-370. Tangpricha, V. et al. (2002). Vitamin d insufficiency among free-living healthy young adults. Am J Med., 112(8), 659-62.

7.  Reduces intestinal absorption of calcium and phosphorus; increases PTH  Secondary Hyperparathyroidism: mineralization defect  Osteopenia/Osteoporosis  Low skeletal calcium  Rickets/Osteomalacia  Low phosphorus  Muscle weakness  Standing/walking/falls

9. › Cancer › CV disease › Diabetes › Autoimmune disorders › Infectious Diseases › more

10.  IOM: › At least 14 scientists, broad range expertise › Assisted by experienced IOM staff members › Public input  Endo Soc Task Force: › Dr Michael Holick, MD › 6 additional experts › 1 methodologist › Medical writer › Member review

11. IOM  Prevalence OVERESTIMATED  Potential harm from overtreatment ENDO SOC  Prevalence UNDERESTIMATED, everyone at risk  IOM report is a POPULATION model, not intended to direct treatment Both agree that there is NOT ENOUGH DATA to support beyond BONE HEALTH

13.  Biomarker of EXPOSURE › Reflection of SUPPLY › use to evaluate INTAKE  Biomarker of EFFECT › Using level as CAUSE and/or PREDICTOR for health outcomes

14.  Factors Affecting Vitamin D levels: › Diet intake (food/supplements) › Dose size/frequency › Sun exposure  Time of day, season, skin pigment, latitude, sunscreen use, clothing, pollution, cloud cover, altitude › Adiposity › Ancestry, especially African

15.  PTH is inconsistent marker › Affected by renal function, exercise level, time of day, diet › No consensus of optimal level to reduce PTH or to prevent rise  The interrelation of Vitamin D & calcium › Can we truly separate/differentiate?

16.  Assay used › Different types of assays  Radioimmunoassay  high-performance liquid chromatography  liquid chromatography tandem mass spectroscopy › What is being measured? › Results not standardized, different parameters of “normal”  20-100 ng/mL

17.  No systematic, evidenced-based process currently exists for determining 25(OH)D cut points that clearly define Vitamin D DEFICIENCY › Use of higher than appropriate cut points will artificially increase the estimated prevalence of Vitamin D deficiency and increase the risk for harm.

18. Based on the available data …

19.  Scientifically proven, cause-effect relationship:  SKELETAL HEALTH

20. INSTITUTE OF MEDICINE 2010  Sufficient: ~ 20 (97.5%)  Insufficient: 12 - < 20  Deficient: < 12  SEs/toxicity/pot harm: > 50  >30 is NOT consistently associated with increased benefits  U-shaped curve ENDOCRINE SOCIETY 2011  Sufficient: ≥ 30  Insufficient: 20-29  Deficient: <20  Optimal: 40-60

21.  0-12 months: 400 IU  1 year -70 years: 600 IU  >70 years: 800 IU  Pregnant/breastfeeding: 600 IU

22.  0-12 months: ≥400 IU  1-18 yrs: ≥ 600 IU (1000)  ≥19 yrs: ≥ 1000 IU (1500-2000)  Pregnant/breastfeeding: ≥ 1000 IU (≥ 1500)

23. Selected food sources of vitamin D Food Sources Vitamin D (IU) 1 Egg 20 Salmon, 3.5 ounces 360 farmed 1000 wild Mackerel, 3.5 ounces 345 Tuna, canned, 3.5 ounces 200 Mushrooms, 100 gm 100 Milk, fortified, 8 ounces100 Breakfast cereals, fortified, 1 serving40–100 Orange juice, fortified, 8 ounces100 Source: Office of Dietary Supplements, National Institutes of Health

24.  Arms and legs for 5-30 minutes › Depends on time of day, season, pigmentation, latitude  10 am – 3 pm  Twice a week  20,000 IU  Tanning beds  SKIN CANCER RISK!

25. Daily Dosage (IU)Expected serum level increase after 3 months (ng/mL) 1001 2002 4004 8008 1,00010 2,00020  D3 preferred (chemically similar, more effective)  BUT D2 is acceptable  Fat soluble, take with meal/snack containing fat

26.  0-18 yrs › 2000 IU/day or 50K IU/week x 6 weeks  >18 yrs: › 6000 IU/day or 50K IU/week x 8 weeks  Obese, malabsorption, meds › 2-3x MORE › 4000-10,000 IU/day

27.  Elderly  Reduced sun exposure › Darker Skin › Institutionalized/Homebound › Sunscreeen use  Breastfed infants  Renal & Liver Disease  GBP/malabsorption  Drugs (PTN, phenobarb, glucocorticoids, etc)  Overweight/obese ALMOST EVERYONE SHOULD BE SCREENED!

29.  Large-scale, RCT  Health outcomes/related conditions  Adverse effects/toxicity/safety  Physiology and molecular pathways  Synthesis of evidence and research methodology  Dose-response relationships  Sun exposure  Intake assessments (assays)

30. Until then …

31.  Counsel patients › Not to self-treat › Take per your CLEAR instructions › Limited supplies, no automatic refills › Careful with calcium intake  Monitor › Labs periodically  After 6-8 weeks therapy  Seasonal late fall/early winter