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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.
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?
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
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
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% probabilityrange: 2,600–5,000 mg/day)
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% 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
CU ORC
THE DRI PROCESS (IN THEORY) first, the consequences of inadequate and
excessive intakes are defined
15
CU ORC
NUTRIENT RESPONSE CURVE*
Intake of Nutrient
Risk
of D
efic
ienc
y
Risk
of T
oxic
ity
UL
RDA
EAR
*DRI book; IOM (2006)
CU ORC
BACKGROUND GUIDANCE
this U-shaped (or J-shaped) distribution of risk is explicitly cited in the IOM’s guidance documents (p. 12)
17
CU ORC
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
CU ORC
THE DRI PROCESS (IN THEORY) first, the consequences of inadequate and
excessive intakes are defined
the focus is on harm, not on benefit
19
CU ORC
the focus is on harm, not on benefitavoiding
^
THE DRI PROCESS (IN THEORY) first, the consequences of inadequate and
excessive intakes are defined
20
CU ORC
the focus is on harm, not on benefitavoiding
^
THE DRI PROCESS (IN THEORY) first, the consequences of inadequate and
excessive intakes are defined
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
CU ORC
RISK AT BOTH EXTREMES
Intake
Risk
of H
arm
deficiencytoxicity
22
CU ORC
THE DRI PROCESS first, the consequences of inadequate and
excessive intakes are defined data describing intakes needed to avoid
those consequences are gathered
23
CU ORC
THE DRI PROCESS first, the consequences of inadequate and
excessive intakes are defined data describing intakes needed to avoid
those consequences are gathered an intake just sufficient to avoid inadequacy
is defined as the requirement
24
CU ORC
NUTRIENT RESPONSE CURVE*
Intake of Nutrient
Risk
of D
efic
ienc
y
Risk
of T
oxic
ity
*DRI book; IOM (2006)
CU ORC
THE SIGMOID RESPONSE
INTAKE
RESPO
NSE
BEN
EFI
T
CU ORC
THE SIGMOID RESPONSE
INTAKE
RESPO
NSE
BEN
EFI
T
minimum daily requirement
CU ORC
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
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)
29
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
30
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
31
CU ORC
THE DRI PROCESS
an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA
32
CU ORC
THE DRI PROCESS
an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA
how is it “estimated” ?
33
CU ORC
THE DRI PROCESS
an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA
how is it “estimated” ? the DRI book says that is to be the average
intake observed in a healthy population
34
CU ORC
THE DRI PROCESS
an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA
how is it “estimated” ? the DRI book says that is to be the average
intake observed in a healthy population
35
CU ORC
THE DRI PROCESS
an Adequate Intake (AI) is an intake “estimated” when there are not sufficient data to calculate the EAR or RDA
how is it “estimated” ? the DRI book says that is to be the average
intake in a healthy population
36
CU ORC
THE SODIUM DRIs the adverse effect with increasing salt
intake, which the AI seeks to minimize, is elevated blood pressure
37
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
38
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
39
CU ORC
Intake
Risk
of H
arm
RISK AT BOTH EXTREMES
toxicity
BP is
the p
roxy
40
CU ORC
Intake
Risk
of H
arm
RISK AT BOTH EXTREMES
presumption: any decrease in intake decreases risk or severity of cardiovascular disease at all salt intakes
BP
is t
he
pro
xy
41
CU ORC
Intake
Risk
of H
arm
RISK AT BOTH EXTREMES
real risk reduction up here
BP
is t
he
pro
xy
42
CU ORC
Intake
Risk
of H
arm
RISK AT BOTH EXTREMES
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
CU ORC
STARTING INTAKE MATTERS
Intake
Risk
of H
arm
H
ealt
h o
utc
om
es a
re t
he
pro
xy
45
CU ORC
STARTING INTAKE MATTERS
Intake
Risk
of H
arm
H
ealt
h o
utc
om
es a
re t
he
pro
xy
46
CU ORC
STARTING INTAKE MATTERS
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
CU ORC
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
CU ORC
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
CU ORC
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
CU ORC
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
CU ORC
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
CU ORC
DASH-I: Conclusions
BP reduction was as large as produced by standard anti-hypertensive mono-therapy regimens
60
CU ORC
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 %
61
CU ORC
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 %
62
CU ORC
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
CU ORC
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
CU ORC
DASH – “OFFICIAL” CONCLUSIONS
emphasis remained on reducing fat and sodium role of increasing Ca & K intakes
minimized or ignored entirely
65
CU ORC
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
CU ORC
THE NUTRIENT PROBLEM the field lacks a consensus on how to define
“normal” or “adequate”
69
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
70
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
71
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
72
CU ORC
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
CU ORC
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
RAAS – A RESCUE MECHANISM
angiotensinogen
renin
angiotensin I
renal blood flow
76
RAAS – A RESCUE MECHANISM
angiotensinogen
renin
angiotensin I angiotensin II
ACE
renal blood flow
77
RAAS – A RESCUE MECHANISM
sympathetic activity
NaClreabsorption & water retention
aldosterone secretion
arteriolar constriction & rise in BP
ADH secretion from pituitary
angiotensinogen
renin
angiotensin I angiotensin II
ACE
renal blood flow
78
RAAS – A RESCUE MECHANISM
sympathetic activity
NaClreabsorption & water retention
aldosterone secretion
arteriolar constriction & rise in BP
ADH secretion from pituitary
angiotensinogen
renin
angiotensin I angiotensin II
ACE
renal blood flow
79
RAAS – A RESCUE MECHANISM
sympathetic activity
NaClreabsorption & water retention
aldosterone secretion
arteriolar constriction & rise in BP
ADH secretion from pituitary
angiotensinogen
renin
angiotensin I angiotensin II
ACE
renal blood flow
80
RAAS – A RESCUE MECHANISM
sympathetic activity
NaClreabsorption & water retention
aldosterone secretion
arteriolar constriction & rise in BP
ADH secretion from pituitary
angiotensinogen
renin
angiotensin I angiotensin II
ACE
renal blood flow
81
CU ORC
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
CU ORC
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
83
CU ORC
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
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
CU ORC
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
CU ORC
A BETTER BENCHMARK the NaCl requirement in patients with RAAS
disabled is the intake that maintains BP without compensatory adjustments
87
CU ORC
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
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 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
CU ORC
CONCLUSIONS the risk curve for Na is the same as for other
nutrients: U-shaped
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
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
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
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
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
Sodium: Too much, too little or just right?
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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Sylvia Escott-Stump, MA, RD, LDNDirector, Dietetic Internship
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Date: January 15, 20152-3 pm EST/1-2 pm CST
www.ConAgraFoodsScienceInstitute.com
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Sodium: Too much, too little or just right?