1. November 5, 2015 Presenter: Robert P. Heaney, MD, FACP, FASN John A. Creighton University Professor & Professor of Medicine Creighton University Osteoporosis Research Center Moderator: James M. Rippe, MD – Leading cardiologist, Founder and Director, Rippe Lifestyle Institute Approved for 1 CPE (Level 2) by the Commission on Dietetic Registration, credentialing agency for the Academy of Nutrition and Dietetics. NUTRI-BITES ® Webinar Series Vitamin D and Calcium New Research - New Recommendations? Original recording of the November 5, 2015 webinar and PDF download of presentation available at: www.ConAgraFoodsScienceInstitute.com

2. Learning Objectives  Recall the principal roles vitamin D and calcium serve in the human body  Describe how nutrients – and vitamin D in particular – are like preventive maintenance of a complex machine  Describe some of the consequences of inadequate intake of each nutrient  List the principal sources of vitamin D and calcium  Recall the optimal intake/input of each nutrient, with emphasis on differing needs at different life stages NUTRI-BITES ® Webinar Series Vitamin D and Calcium: New Research-New Recommendations

3. CU ORC TWO FRAMEWORKS: 3 The nutrient requirement Risk assessmentPhysiology Avoidance of some disease outcome Support of cell function

4. CU ORC RECOMMENDATION DISCORDANCE Ages 51–70:  IOM 2010  Endo Soc 2010  Am Ger Soc 2014  GrassrootsHealth Daily Input (IU) RDA/AITUIL 6004,000 1,500–2,00010,000 4,000-- 4,000–5,000–– 4

5. low Ca absorption elevated PTH production elevated 1,25(OH) 2 D production  Ca absorption Elevated PTH is an index of Ca and/or vitamin D inadequacy The rise in PTH doesn’t cause us to consume more Ca, but it does cause us to absorb more, thus tending to close the loop

6. CU ORC THE SETPOINT CRITERION With a physiological criterion, “normal” vitamin D status would be a 25(OH)D concentration that required little or no compensatory PTH response under basal conditions.  data from NHANES 2003-2006  N = 14,681  Ginde etal., J. Endocrinol. Invest. (2011)

7. 7 Compensation is metabolically costly and often takes a toll in other organ systems. Over the course of the evolution of human physiology, natural selection would have favored organisms that did not have to compensate for what the environment provided.

8. 8 Ancestral Intakes of Vitamin D Just because ancestral humans averaged ~115 nmol/L doesn’t automatically mean that modern humans need that much.  But that’s the best starting point  in determining the requirement, the burden of proof should fall on those who say lower 25(OH)D values are adequate (and safe).  the question of adequacy must be: Will lower levels support critical physiological activities?

9. Supporting a critical physiological function

10. CU ORC LACTATION FACTS  human milk is capable of providing all the vitamin D (cholecalciferol) an infant needs  but only if the mother has native vitamin D (cholecalciferol) in her blood  cholecalciferol crosses from the blood into the milk, but 25(OH)D does not  so serum cholecalciferol is the key variable  its concentration begins to rise only after the hepatic 25-hydroxylase is approximately saturated, and that corresponds to a serum 25(OH)D above 100 nmol/L (40 ng/mL) 10

11. CU ORC SUMMARY – Vitamin D  vitamin D remains a nutrient of concern  in pregnant women  in babies in utero  in infants  low perinatal vitamin D status leads to several late-life consequences  serum 25(OH)D levels should be maintained at 40 ng/mL or above 11

12. CU ORC Bone Health and Osteoporosis A Report of the Surgeon General 12 “Calcium has been singled out as a major public health concern today because it is critically important to bone health and the average American consumes levels of calcium that are far below the amount recommended for optimal bone health.” October 14, 2004 the typical postmenopausal woman in the U.S. consumes slightly less than 1 cup milk/day by contrast, the DGA recommends 3 dairy servings/day

13. CU ORC CONSENSUS CONFERENCES  three NIH Consensus Development Conferences had specifically recommended Ca supplements:  1984 – Osteoporosis  1994 – Optimal Ca Intake  2000 – Osteoporosis 13

14. CU ORC DANGERS WITH CALCIUM?  haven’t there been some papers suggesting increased CVD risk with Ca supplements?  Yes,  but these papers have been thoroughly refuted and, as it turns out, high Ca intakes are actually associated with reduced all-cause mortality 14

15. CU ORC DIET CALCIUM AND MORTALITY  23,366 Swedish men  10-yr prospective study  2358 deaths  highest Ca intake tertile compared to lowest  Kaluza et al., Am J Epidemiol 2010, 171:801–7 15 mean Ca intakes: lowest tertile – 990 mg/d (± 187) highest tertile – 1953 mg/d (± 334)

16. CU ORC RESTORING PRE-MENOPAUSAL RATES  the importance of restoring premenopausal rates of remodeling is shown by the fact that potent bisphosphonates produce the same reduction in fracture risk in patients who experience no change in BMD as in those who show an increase in BMD  the bone-sparing effect of bisphosphonates is of minor importance, despite the fact that bone sparing is generally considered the basis for their effect 16 Elevated bone remodeling is the principal cause of fragility in postmenopausal women with osteoporosis, and should be the principal target of fracture protection strategies

17. CU ORC 17 CALCIUM, VIT D, & FRACTURE Dawson-Hughes et al., NEJM 1997:337:670-6 Ca + Vit D placebo –55%  the effect begins immediately  because remodeling reduction begins immediately

18. CU ORC SUMMARY – VITAMIN D  vitamin D is essential for adequate functioning of virtually all body systems  inadequate vitamin D status predisposes to various chronic diseases  optimal status is achieved when serum 25(OH)D is between 40 and 60 ng/mL  this requires an all-source input of ~5000 IU/d 18

19. SUMMARY – CALCIUM  Calcium is still important in 2015  optimal intake : 1200–1800 mg/d  preferably from dairy  bone protection is due largely to reduction of excess bone remodeling 19

20. CU ORC Take away messages....  Most Americans have inadequate intakes of both vitamin D and Ca.  Foods are the best sources for the needed Ca  But vitamin D needs can best be met by a combination of sun exposure and supplements 20

21. CU ORC ADDITIONAL RESOURCES  Vitamin D:  Baggerly C. et al. (2015) Sunlight & Vitamin D: Necessary for Public Health J Am Coll Nutr  Heaney RP & Armas LAG (2015) Quantifying the Vitamin D Economy. Nutr Rev  Calcium:  Surgeon General’s Report: Bone Health & Osteoporosis (2004)  Heaney RP (2003) Is the paradigm shifting? Bone 21