1. November 6, 2014 Presenter: Robert P. Heaney, MD John A. Creighton University Professor/Professor of Medicine Creighton University 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 Sodium: Too much, too little or just right? Original recording of the November 6, 2014 webinar and PDF download of presentation available at: www.ConAgraFoodsScienceInstitute.com

2. Based on this webinar the participant will be able to:  Review the evolution of sodium intake recommendations  Understand the physiology related to regulating sodium metabolism  Discuss latest findings of the association of sodium intake to health outcomes  Outline practical dietary strategies dietitians can offer clients as the science on sodium evolves NUTRI-BITES ® Webinar Series Sodium: Too much, too little or just right?

3. CU ORC SOME SODIUM INTAKE FACTS  2004 IOM recommendations for adults: < 1,500 mg/day up to age 50 < 1,300 mg/day from 50 to 70 < 1,200 mg/day after age 70  mean Na intake in U.S. & Europe: 3,450 mg/day (95% probability range: 2,600–5,000 mg/day)  this intake has been stable for at least 50 years in forty five 1 st world nations

4. CU ORC NUTRIENT RESPONSE CURVE* UL RDA EAR * DRI book; IOM (2006)

5. CU ORC RISK AT BOTH EXTREMES 5   deficiency toxicity

6. CU ORC THE DRI PROCESS  first, the consequences of inadequate and excessive intakes are defined  data describing intakes needed to avoid those consequences is gathered  an intake just sufficient to avoid inadequacy is defined as the requirement  recognizing that individuals will have differing requirements, an average requirement is estimated (the EAR) 6

7. CU ORC THE SODIUM DRIs  the IOM noted that Na effects arose not from Na, per se, but from NaCl, the form in which ~90% of ingested Na enters the body  the IOM stated that there was not enough evidence regarding NaCl effects to establish the usual DRIs, and so proposed, instead, an AI 7

8. CU ORC THE SODIUM DRIs  the adverse effect with increasing salt intake, which the AI seeks to minimize, is elevated blood pressure  the IOM, in effect, ignored adverse effects at low intakes, i.e., the panel used a linear model rather than a U-shaped model  this explains why the BP data and the health outcomes data disagree 8

9. CU ORC STARTING INTAKE MATTERS 9   Health outcomes are the proxy

10. CVD RISK vs. Na INTAKE  17 country study  N = 101,945  mean follow- up: 3.7 years  O’Donnell et al. NEJM 371:612 (2014) 10

11. CU ORC 11 DASH–I*  three-way trial of dietary intervention  standard American diet  diet high in fruits and vegetables  diet high in fruits & vegetables plus low- fat milk (~730 mg extra Ca)  Na intake held constant at ~3000 mg across all three diets *Appel et al., NEJM 1997; 336:1117-24

12. CU ORC 12 DASH-I: Conclusions  BP reduction was as large as produced by standard anti-hypertensive mono- therapy regimens  if applied at a population level, the full DASH diet would reduce incidence of  stroke by 27 %  MIs by 15 %

13. CU ORC 13 DASH – ANOTHER CONCLUSION  the possibly harmful effects of high Na intake are magnified when the diet is inadequate in Ca and K  high Ca & K intakes mitigate the possible harm of high Na intakes

14. CU ORC THE NUTRIENT PROBLEM  the field lacks a consensus on how to define “normal” or “adequate”  that leaves the field virtually without a target to aim at  and forces reliance upon empirical evidence that, e.g., intake A is “better” by some measurable endpoint than intake B  the evidence must be in the form of RCTs 14

15. RAAS – A RESCUE MECHANISM  sympathetic activity  NaCl reabsorption & water retention  aldosterone secretion  arteriolar constriction & rise in BP  ADH secretion from pituitary 15 angiotensinogen renin angiotensin I angiotensin II ACE  renal blood flow... but notice: when you reduce Na intake below a critical level, you activate mechanisms that try to raise BP

16. CU ORC RISK CURVE FOR BP LOWERING  5-yr non- concurrent cohort study  398,419 hypertensive pts. at Kaiser SoCal  risk of death &/or ESRD  Sim et al., J Am Coll Cardiol 2014; 64:588–97

17. CU ORC CONCLUSIONS  the risk curve for Na is the same as for other nutrients: U-shaped  risk of harm rises at both extremes of intake  the lowest risk range seems to be at about the current U.S. average Na intake  there is no evidence to justify efforts to decrease average salt intake  we should be emphasizing increasing Ca and K intakes, rather than decreasing Na intake