sodium: too much, too little or just right?...webinar logistics ceus – a link to obtain your...

November 6, 2014

Presenter:

Robert P. Heaney, MDJohn A. Creighton University Professor/Professor of Medicine

Creighton UniversityModerator:

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?

ConAgra Foods Science Institute With a mission of:

Promoting dietary and related choices affecting wellness

by linking evidence-based understanding

with practice

Webinar logistics CEUs – a link to obtain your personalized Continuing

Education Credit certificate will be emailed within 2 days.

A recording of today’s webinar, slides, and summary PowerPoint will be available to download as a PDF within 2 days at: www.ConAgraFoodsScienceInstitute.com

The presenter will answer questions at the end of this webinar. Please submit questions by using the ‘Chat’ dialogue box on your computer screen.

http://www.conagrafoodsscienceinstitute.com/

Today’s Faculty

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

Learning Objectives

After the 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?

Robert P. Heaney, MD, FACP, FASN

Creighton University Osteoporosis Research Center

Disclosures for: Robert P Heaney, M.D.

AFFILIATION/FINANCIAL INTERESTS

CORPORATE ORGANIZATION

Grants/Research Support: none

Scientific Advisory Board/Consultant:

Int’l Dairy Foods Assn.

Speakers Bureau: none

Stock Shareholder: none

Other Financial or Material Support/Honorarium:

none

TIME: March 15, 19829

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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

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mean Na intake in U.S. & Europe:3,450 mg/day (95% probabilityrange: 2,600–5,000 mg/day)

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mean Na intake in U.S. & Europe:3,450 mg/day (95% probabilityrange: 2,600–5,000 mg/day)

this intake has been stable for at least 50 years in forty five 1st world nations

SODIUM INTAKE OVER TIME*

13 population-based studies in the UK

N = 6,343 1984 – 2008

McCarron et al., CJASN 2009

Year Assessed1985 1990 1995 2000 2005 2010

Uri

ne N

a (m

mol

/d)

80

100

120

140

160

180

200

220

mean: 150.4 (3450 mg)

– 2 SEM

+ 2 SEM

13

How, in theory, are Dietary Reference Intakes (DRIs) determined?

14

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THE DRI PROCESS (IN THEORY) first, the consequences of inadequate and

excessive intakes are defined

15

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NUTRIENT RESPONSE CURVE*

Intake of Nutrient

Risk

of D

efic

ienc

y

Risk

of T

oxic

ity

UL

RDA

EAR

*DRI book; IOM (2006)

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BACKGROUND GUIDANCE

this U-shaped (or J-shaped) distribution of risk is explicitly cited in the IOM’s guidance documents (p. 12)

17

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BACKGROUND GUIDANCE

this U-shaped (or J-shaped) distribution of risk is explicitly cited in the IOM’s guidance documents (p. 12)

and is taken as the basic model for all nutrients in standard textbooks of nutritional epidemiology

18

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the focus is on harm, not on benefit

19

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the focus is on harm, not on benefitavoiding

^



20

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the focus is on harm, not on benefitavoiding

^



a reversion back to the prevailing medical paradigm of the 1st quarter of the 20th

century: all diseases are caused by foreign agencies – microbial or toxic

21

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RISK AT BOTH EXTREMES

Intake

Risk

of H

arm

deficiencytoxicity

22

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THE DRI PROCESS first, the consequences of inadequate and

excessive intakes are defined data describing intakes needed to avoid

those consequences are gathered

23

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those consequences are gathered an intake just sufficient to avoid inadequacy

is defined as the requirement

24

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NUTRIENT RESPONSE CURVE*

Intake of Nutrient

Risk

of D

efic

ienc

y

Risk

of T

oxic

ity

*DRI book; IOM (2006)

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THE SIGMOID RESPONSE

INTAKE

RESPO

NSE

BEN

EFI

T

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THE SIGMOID RESPONSE

INTAKE

RESPO

NSE

BEN

EFI

T

minimum daily requirement

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SERUM 25(OH)D (nmol/L)

0 20 40 60 80 100 120 140 160

ABSO

RPT

ION

FR

AC

TIO

N

0.0

0.1

0.2

0.3

0.4

0.5

A VITAMIN D THRESHOLD

CALC

IUM

28

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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)

29

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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

30

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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

31

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THE DRI PROCESS

an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA

32

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THE DRI PROCESS


how is it “estimated” ?

33

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THE DRI PROCESS


how is it “estimated” ? the DRI book says that is to be the average

intake observed in a healthy population

34

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THE DRI PROCESS



intake observed in a healthy population

35

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THE DRI PROCESS



intake in a healthy population

36

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THE SODIUM DRIs the adverse effect with increasing salt

intake, which the AI seeks to minimize, is elevated blood pressure

37

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the IOM, in effect, ignored adverse effects at low intakes, i.e., the panel used a linear model rather than a U-shaped model

38

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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

39

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Intake

Risk

of H

arm


toxicity

BP is

the p

roxy

40

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Intake

Risk

of H

arm


presumption: any decrease in intake decreases risk or severity of cardiovascular disease at all salt intakes

BP

is t

he

pro

xy

41

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Intake

Risk

of H

arm


real risk reduction up here

BP

is t

he

pro

xy

42

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Intake

Risk

of H

arm


real risk reduction up here

is applied down here

BP

is t

he

pro

xy

43

“You can say without any shadow of doubt” that the authorities pushing the eat-less-salt message had “made a commitment to salt education that goes way beyond the scientific facts.”

Drummond Rennie, M.D.Editor, JAMA

44

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STARTING INTAKE MATTERS

Intake

Risk

of H

arm

H

ealt

h o

utc

om

es a

re t

he

pro

xy

45

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Intake

Risk

of H

arm

H

ealt

h o

utc

om

es a

re t

he

pro

xy

46

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Intake

Risk

of H

arm

H

ealt

h o

utc

om

es a

re t

he

pro

xy

47

CVD EVENTS*

0

5

10

15

20

25

1st 2nd 3rd 4th

CVD

MIN = 2937

CV

D/1

000

pers

on y

ears

UNa+ Quartiles

*Worksite Hypertension Study; Alderman, M. 1995 Hypertension 25:1144–5248

CVD EVENTS*

0

5

10

15

20

25

1st 2nd 3rd 4th

CVD

MIN = 2937

CV

D/1

000

pers

on y

ears

UNa+ Quartiles

*Worksite Hypertension Study; Alderman, M. 1995 Hypertension 25:1144–52

> 4000 mg< 2000 mg

49

CV MORTALITY & MORBIDITY*

*Stolarz-Skrzypek et al., JAMA 2011 [pooled data from two large European studies]

CVD Mortality All CVD Events

50

TYPE I DIABETES & MORTALITY*

*Thomas et al., Diabetes Care 2011

“Normal“ Range

Current (AI) Recommendation

2800–5000 mg/d

51

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RISK vs. INTAKE

composite of CV death, stroke, MI, & CHF

14 cohort studies N = 154,282 O’Donnell et al.,

Eur Heart Journal 2012

Urine Na (g/d)0 2 4 6 8 10 12

Haz

ard

Rati

o (9

5% C

I) 2.2

2.6

1.8

1.4

1.0

0.6

0.8

52

CU ORCUrine Na (g/d)

0 2 4 6 8 10 12

Haz

ard

Rati

o (9

5% C

I)

RISK vs. INTAKE

combined CV death, stroke, MI, & CHF

O’Donnell et al., Eur. Heart Journal 2012

2.2

2.6

1.8

1.4

1.0

0.6

0.8lowest risk

53

CHF RISK vs. Na INTAKE

EPIC-Norfolk Study

n = 19,857 mean follow-up:

12.9 yrs Pfister et al.

(2014) Eur J Heart Failure

Urine Sodium (mmol/d)50 100 150 200 250

ln[A

dj. H

azar

d Ra

tio]

-0.6

-0.4

-0.2

0.0

0.2

0.4

0.6

lowest risk

54

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)

Sodium Excretion (g/day)0 2 4 6 8 10 12

Odd

s Ra

tio

1.0

1.5

2.0

2.5

3.0

55

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FURTHER PROBLEMS

besides using a linear model instead of a U-shaped one, the IOM failed to factor in the crucial roles of Ca and K intakes, as revealed in the classic DASH studies

56

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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)

*Appel et al., NEJM 1997; 336:1117-24

57

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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

58

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DASH–I: Hypertensive Cohort*Control F&V F&V + Dairy

∆ D

iast

olic

BP (

mm

/Hg

)

-6

-4

-2

0

*Appel et al., NEJM 1997; 336:1117-24

59

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DASH-I: Conclusions

BP reduction was as large as produced by standard anti-hypertensive mono-therapy regimens

60

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DASH-I: Conclusions


if applied at a population level, the full DASH diet would reduce incidence of

stroke by 27 %

MIs by 15 %

61

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DASH-I: Conclusions


if applied at a population level, the full DASH diet would reduce incidence of

stroke by 27 %

MIs by 15 %

62

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DASH–II

Control

DASH

standard diet, but with three levels of Na intake

high fruit, vegetable, and dairy diet, also with three levels of Na intake

63

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Na, BP, & THE DASH DIET*

Sodium Intake Level (mg/d)3300 2400 1500

Mea

n Sy

stol

ic B

P (m

m H

g)

120

125

130

135

140

DASH

Control

*Vollmer et al. AIM 2001:135:1019–102864

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DASH – “OFFICIAL” CONCLUSIONS

emphasis remained on reducing fat and sodium role of increasing Ca & K intakes

minimized or ignored entirely

65

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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

66

NUTRITION IS LIKE AN ORCHESTRA

calcium magnesiumvitamin D

potassium sodium

Sodium is a “poster child” for the larger nutrient

problem

68

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THE NUTRIENT PROBLEM the field lacks a consensus on how to define

“normal” or “adequate”

69

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“normal” or “adequate” that leaves the field virtually without a target

to aim at

70

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to aim at and forces reliance upon empirical evidence

that, e.g., intake A is “better” by some measurable endpoint than intake B

71

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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

72

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OTHER BENCHMARKS there are several alternative benchmarks

that have been proposed the one that seems best for Na is the

intake that minimizes the need for the physiological compensation that occurs when Na intake is low

73

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A BETTER BENCHMARK such compensation, for Na, is the activation

of the RAAS mechanism, which becomes operative at Na intakes at or below ~3000 mg/d for an adult

74

RAAS – A RESCUE MECHANISM

angiotensinogen

75


angiotensinogen

renin

angiotensin I

renal blood flow

76


angiotensinogen

renin

angiotensin I angiotensin II

ACE

renal blood flow

77


sympathetic activity

NaClreabsorption & water retention

aldosterone secretion

arteriolar constriction & rise in BP

ADH secretion from pituitary

angiotensinogen

renin


ACE

renal blood flow

78







angiotensinogen

renin


ACE

renal blood flow

79







angiotensinogen

renin


ACE

renal blood flow

80







angiotensinogen

renin


ACE

renal blood flow

81

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Na INTAKE & RAAS RESPONSES*

*Brunner et al., NEJM (1972) 286:441–49

Urine Sodium (mmol/d)0 100 200 300Pl

asm

a Re

nin

Activ

ity (n

g/m

L/hr

)

0

2

4

6

8

10

12

14

Urine Sodium (mmol/d)0 100 200 300

Aldo

ster

one

(g/

d)0

20

40

60

80

100

120

82

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asm

a Re

nin

Activ

ity (n

g/m

L/hr

)

0

2

4

6

8

10

12

14


Aldo

ster

one

(g/

d)0

20

40

60

80

100

120

83

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asm

a Re

nin

Activ

ity (n

g/m

L/hr

)

0

2

4

6

8

10

12

14


Aldo

ster

one

(g/

d)0

20

40

60

80

100

120

84

0

10

20

30

40

Low

Normal

High

LowModerate

High

MIs

per

100

0 Pe

rson

-Yea

rs

Renin

Leve

l

Risk Level

MI RISK & RENIN LEVELS*

*Alderman, M.NEJM 1991;Am J Hypertension

1997

34.5

7.8

4.8

3.1

20.0

6.5

1.7

2.52.1

85

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A BETTER BENCHMARK such compensation, for Na, is the activation

of the RAAS mechanism, which becomes operative at Na intakes at or below ~3000 mg/d for an adult

using that criterion, Na intakes < 3000 mg would be “deficient”

in other words, without compensation individuals would have hypotension and/or hypovolemia

86

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A BETTER BENCHMARK the NaCl requirement in patients with RAAS

disabled is the intake that maintains BP without compensatory adjustments

87

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A BETTER BENCHMARK the NaCl requirement in patients with with

RAAS disabled is the intake that maintains BP without compensatory adjustments

that’s precisely the situation with Addison’s disease (because those patients lack aldosterone)

thus, the NaCl intake needed in pts. with adrenal insufficiency is arguably the best estimate of “optimal” for everybody

88

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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 CollCardiol 2014; 64:588–97

Systolic Blood Pressure

<110

110–120

120–130

130–140

140–150

150–160

160–170>170

Adj

uste

d H

azar

d Ra

tio

0

1

2

3

4

5

6

7

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CONCLUSIONS the risk curve for Na is the same as for other

nutrients: U-shaped

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nutrients: U-shaped risk of harm rises at both extremes of intake

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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

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current U.S. average Na intake there is no evidence to justify efforts to

decrease average salt intake

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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

Questions?

95

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


ConAgra Foods Science Institute Nutri-Bites® Webinar details

A link to obtain your Continuing Education Credit certificate will be emailed within 2 days

Today’s webinar will be available to download within 2 days at: www.ConAgraFoodsScienceInstitute.com

For CPE information: [email protected]

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