FENS 2019 - Dublin Dietary Reference Values for Sodium, Prof. A Naska

1. Dietary Reference
Values for sodium:
challenges and
opportunities
Androniki Naska
National and Kapodistrian University of
Athens, School of Medicine
Chair of the EFSA Working Group on Dietary
Reference Values for minerals
16 October 2019

2. Sodium, a challenging nutrient
3
 Sodium is an essential nutrient and is needed by the body
 Sodium intake has been associated with increased blood pressure and risk of CVD
Is there an adequate and safe range of intake for sodium?
 Universal salt reduction has been the subject of scientific controversy
 Polarization of the scientific literature on sodium intakes and health outcomes
 Conclusions of systematic reviews on the topic are diverging
PROPONENTS
“High sodium intakes increase blood pressure,
thus, the risk of cerebro-cardiovascular events”
“Salt reduction policies will produce major
public health benefits”
OPPONENTS
“Relationship between sodium intake and
clinical outcomes is U- or J-shaped”
“The harms associated with low sodium intakes
may mitigate any potential benefits of blood
pressure reduction”

3. EFSA Prometheus
4
 EFSA Prometheus approach
(PROmoting METHods for
Evidence Use in Scientific
assessments)
http://www.efsa.europa.eu/interactive_pages/
prometheus/prometheus

4. Process
2016 –
2017
• Drafting of the background sections of the Opinion
• Protocol development
• Protocol published (ZENODO and PROSPERO)
2018
• Protocol implementation
2019
• Opinion finalisation, adoption
• Publication
• EFSA Journal
• Amended protocol published (ZENODO and PROSPERO)
Public
consultation
Public
consultation
+ technical
meeting
Open plenary
Dietary reference values for sodium,
Published in EFSA Journal on September 4, 2019
https://www.efsa.europa.eu/en/efsajournal/pub/5778

5. Methodological steps (adults)
6DRVs for sodium
Data integration
Expert Knowledge Elicitation (EKE)
BIOMARKERS AS
INDICATORS OF
REQUIREMENTS
No useful marker
SODIUM AND HEALTH CONSEQUENCES
Literature search
Study selection
(title/abstract and full text screening)
Risk of bias
appraisal
Data extraction
Data analysis
(Meta-analyses, meta-regression where possible)
Problem formulation
SODIUM BALANCE
Literature search
Study selection
Assessment of
the evidence
Problem formulation
Uncertaintyanalysis
BIOMARKERS OF
INTAKE
24-hour urinary
sodium excretions

6.  Evidence
 Metabolic studies that inform about systemic mechanisms to maintain a Na balance.
 Several studies excluded because of methodological limitations
 3 studies in adults and 1 study in adolescents were thoroughly reviewed
 Findings
 Balance maintained over a wide range of Na intake
 Mean Na intake assessed in eligible balance studies ranged between 1.5 g and 4.9
g/day in adults and between 1.31 and 3.95 g/day in adolescents.
 Rhythmical variations in the Na body pool independent of Na intake
 Response of sympathetic nervous system and the renin–angiotensin–aldosterone
system to conserve Na evident at excretion below 100mmol/24 hours
 Conclusion
 Balance studies cannot be used to determine Na requirements
 Can be used to inform about the levels of Na intake adequate to maintain a null
balance.
Balance studies
7

7. Prisma chart – BP and CVD
8
Records screened in the basis
of title and abstract (n=7,141)
Full–text articles assessed for
eligibility (n=402)
Studies included in the
qualitative synthesis (n=45)
36 experimental
9 observational
Studies included in
quantitive synthesis (meta–
analysis) (n=32)
Records identified
through database
searching, after
duplicates removed
(n=6,264)
Additional records
identified through
snowballing, after
duplicates removed
(n=877)
Records excluded
(n=6,731)
Systematic reviews (n=8)
Articles excluded, with
reasons (n=357)
IdentificationScreeningEligibilityIncluded

8.  Findings
 Significant effects of Na reduction on SBP by –3.9 mmHg (95%CI: –
5.1, –2.8 mmHg)
 Significant effects of Na reduction on DBP by –2.0 mmHg (95%CI: –
2.8, –1.2 mmHg)
 Linear dose–response over the range of mean UNa observed (49 –
209 mmol/24 h (1.3 – 4.8 g/day))
 Mean SBP increased by 5.3 mmHg (95% CI: 3.6, 6.9 mmHg) for each
100 mmol (2.3 g)/24–h increase in mean UNa
 Mean DBP increased by 2.6 mmHg (95% 1674 CI: 1.6, 3.7 mmHg) for
each 100 mmol (2.3 g)/24–h increase in mean UNa
 Stronger association among hypertensive vs normotensive individuals
and among subjects aged 50 years vs subjects <50 years
Blood pressure in adults
9

9.  Evidence
 1 prospective cohort study (moderate RoB) on the long–term
relationship between UNa and blood pressure levels
 2 RCTs (low RoB) and 2 prospective observational studies (low and
moderate RoB) on the relationship between UNa and risk of
hypertension
 Findings
 Support the positive relationship between UNa and blood pressure
levels
Blood pressure in adults
10

10.  Evidence
 No RCT eligible
 Small number of prospective cohort studies
 3 cohorts on the risk of stroke or on the risk of coronary heart disease
PREVEND (low RoB); EPOGH/FLEMENGHO and the Finnish cohort (moderate RoB)
 3 cohorts on the risk of cardiovascular disease
TOPHI/II (low RoB); EPOGH/FLEMENGHO and InCHIANTI (moderate RoB)
 No quantitative analysis
 Findings
 Limited conclusions
 Risk of coronary heart disease: some evidence for a positive association
 Risk of stroke: some evidence for an inverse association
 Small number of studies and mechanisms unclear
 Risk of cardiovascular disease: some evidence for a positive association
Cardiovascular diseases
12

11.  An average requirement (AR) and a population reference intake
(PRI) can NOT be established for Na, because the distribution of the
requirement cannot be determined
 Data relevant to the setting of DRVs for sodium
 Balance studies: levels of Na intake adequate to maintain a null
balance
 Relationship between Na and blood pressure or CVD risk: levels of
Na associated with a reduced risk of chronic diseases
 Expert judgement, taking account of the associated uncertainties
 Use of a formal Expert Knowledge Elicitation (EKE) process
 Guidance of EFSA published in 2014
Relevant data and integration of the
evidence
13

12.  Formal Expert Knowledge Elicitation (EKE)
 Evidence–based judgements about a quantity of interest
 Judgements expressed about the range of possible values for the quantity of interest
and their relative likelihoods
Limits bias;
Structured process improves rigour of reasoning;
Clear and unambiguous expression of uncertainty;
Rationale documented.
 EKE conducted with the experts of the EFSA WG on DRVs for minerals
 ‘Sheffield’ protocol
 Method designed to elicit the knowledge of a group of experts in a face–to–face
elicitation meeting
 Presence of an elicitor essential.
EKE method
14

13.  Data on Na and blood pressure or CVD risks could inform about
the levels of sodium intake associated to a reduced risk of chronic
diseases
 Balance studies could inform about the levels of sodium intake which
are adequate to maintain a null sodium balance
EKE questions
Question 2 What is the lowest level of sodium intake which is adequate (i.e.
amount which allows to maintain sodium balance) for the majority (≥ 97.5%)
of the general population of adults?
Question 1 What is the lowest level of sodium intake at which the risk of
chronic disease (i.e. stroke, CHD) is minimised in the majority (≥ 97.5%) of
the general population of adults?

14.  What is the lowest level of sodium intake at which the risk of
chronic disease (i.e. stroke, CHD) is minimised in the majority (≥
97.5%) of the general population of adults?
Group consensus uncertainty probability
distribution I

15.  What is the lowest level of sodium intake which is adequate (i.e.
amount which allows to maintain sodium balance) for the
majority (≥ 97.5%) of the general population of adults?
Group consensus uncertainty probability
distribution II

16.  A sodium intake of 2.0 g/day
represents a level of sodium
for which there is sufficient
confidence in a reduced risk of
CVD in the general adult
population.
 A sodium intake of 2.0 g/day
is likely to allow most of the
general population to maintain
sodium balance
 2.0 g of sodium per day is a
safe and adequate intake for
the general EU population of
adults
Conclusion – DRVs for adults
18

17.  Safe:
 the concept of a safe intake has been used in previous assessments regarding a daily
intake of a nutrient which does not give rise to concerns about adverse health
effects, in instances when a tolerable upper intake level (UL) could not be established.
 Adequate:
 An adequate intake (AI) is the value estimated when a population reference intake (PRI)
cannot be established because an average requirement (AR) cannot be determined (EFSA
NDA Panel, 2010).
 The AI is the level of intake that is assumed to be sufficient based on
observations from groups of apparently healthy people.
Terminology
19

18.  Mean/median intake of Na in European populations exceeds the safe and
adequate intakes proposed
 Low risk of inadequate (insufficient) intake in European populations
 Concerns relate to ‘excess’ intake of Na
 For populations: value proposed can be used to inform the setting of population
goals for the reduction of Na intake
 For individuals: if the usual intake of Na exceeds this value, it could be associated
with an increased risk of CVD, including concurring risk factors such as primary
hypertension.
In practice
20

19.  Requirement for the daily accretion rate of sodium in fetal and
maternal tissues can be met by adaptive changes that maintain Na
homeostasis during pregnancy
 No evidence that Na requirement of lactating women differs from the
requirement of non–lactating women
 Lack of data from which an AR could be derived for infants
 Upwards extrapolation from the estimated Na intake of fully breast–fed
infants during the first 6 months of life (120 mg/day)
 Lack of data from which an AR could be derived for children
 Downwards extrapolation from the reference value for adults, based on
the AR for energy and including a growth factor
Conclusions – other population groups

20. Safe and Adequate Intake
(g/day)
1–3 years 1.1
4–6 years 1.3
7–10 years 1.7
11–17 years 2.0
≥ 18 years 2.0
Conclusions
22
Adequate Intake
(g/day)
7–11 months 0.2

21. Contributors
25
 NDA Panel Members
 Dominique Turck (chair)
 Jacqueline Castenmiller
 Stefaan de Henauw
 Karen-Ildico Hirsch-Ernst
 John Kearney
 Helle Katrine Knutsen
 Alexandre Maciuk
 Inge Mangelsdorf
 Harry J McArdle (vice-chair)
 Androniki Naska
 Carmen Pelaez
 Kristina Pentieva
 Alfonso Siani
 Frank Thies
 Sophia Tsabouri
 Marco Vinceti
 EFSA WG on DRVs for minerals
 Androniki Naska (chair)
 Peter Aggett
 Susan Fairweather-Tait
 Ambroise Martin
 Hildegard Przyrembel
 Alfonso Siani
 Marco Vinceti (vice-chair)
 EFSA NUTRI staff
 Agnès de Sesmaisons Lecarré
 Silvia Valtueña Martinez
 Anja Brönstrup (SO)
 Jelena Gudelj Rakic (SNE)
 Olga Vidal Pariente, Qingqing Sun,
Ester Artau Cortacans (trainees)
 Pauline Lachevre (guest scientist)
 EFSA AMU staff
 Laura Ciccolallo
 Elisa Aiassa
 Andrea Bau
 Daniela Tomcikova
 Irene Munoz Guajardo
 EFSA WG on uncertainty analysis
 Andy Hart
 Laura Martino (AMU staff)
 Caroline Merten (SCER staff)

22.  34 opinions published
 Cover protein, carbohydrates,
fats, energy, 14 vitamins and 15
minerals
 Useful resources
 Topic on DRVs on EFSA’s
website
 Special issue on DRVs in EFSA
Journal
 DRVs Finder
DRVs at EFSA
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Poster presentation 8:30-9:15, 17th October Liffey B (Level 1)
Poster Session 2, Station 23, Presentation 2.

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