Review 821

Benefit assessment of salt red

uction in patients withhypertension: systematic overviewEva Matyasa, Klaus Jeitlera,b, Karl Horvatha, Thomas Semlitscha,Lars G. Hemkensc, Nicole Pignittera and Andrea Siebenhoferd

Objective We assessed the benefits and harm of reduced

salt intake in patients with essential hypertension focusing

on patient-relevant outcomes and blood pressure.

Methods A systematic search of five electronic databases

was performed to identify high-quality secondary literature

based on randomized controlled trials (RCTs). An

update primary literature search (RCTs) was performed for

the time period up to 2010 that was not covered by

secondary literature. Major outcomes were death,

cardiovascular morbidity/mortality, hospital stays, terminal

renal failure, quality of life, and adverse events. Change in

blood pressure was defined as surrogate parameter.

Results Four different systematic reviews and two RCTs

met the inclusion criteria. Only one review reported limited

data on patient-relevant outcomes. Over an intervention

period of up to 12 months, mean SBP was reduced by

3.6–8.0 mmHg in all reviews. For the same intervention

period, a statistically significant advantage with regard to

mean DBP reduction ranging from 1.9 to 2.8 mmHg was

found in three reviews. The fourth publication reported a

nonsignificant reduction (DBP reduction of 4.7 mmHg).

None of the RCTs identified in the primary literature search

update reported data on patient-relevant outcomes.

However, both RCTs found blood pressure improvements

with salt reduction.

0263-6352 � 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Conclusion A benefit from a salt-reduced diet in patients

with high blood pressure is not proven with regard to

patient-relevant outcomes based on systematic reviews

and RCTs published up to 2010. The results indicate a blood

pressure-lowering effect through reduced salt intake in

hypertensive patients. J Hypertens 29:821–828 Q 2011

Wolters Kluwer Health | Lippincott Williams & Wilkins.

Journal of Hypertension 2011, 29:821–828

Keywords: diet, dietary, hypertension, sodium, sodium-restricted

Abbreviations: HTA, health technology assessment; IQWiG, Institute forQuality and Efficiency in Healthcare; RCTr, andomized controlled trial

aDepartment of Internal Medicine, EBM Review Center Medical University ofGraz, bInstitute for Medical Informatics, Statistics and Documentation, MedicalUniversity of Graz, Graz, Austria, cInstitute for Quality and Efficiency in Healthcare(IQWiG), Cologne and dInstitute of General Practice, Goethe UniversityFrankfurt, Frankfurt, Germany

Correspondence to Andrea Siebenhofer, MD, Institute of General Practice,Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, GermanyTel: +49 69 6301 7296; fax: +49 69 6301 6428;e-mail: siebenhofer@allgemeinmedizin.uni-frankfurt.de

Received 23 June 2010 Revised 14 December 2010Accepted 28 December 2010

See editorial comment on page 829

Introduction associated with increased cardiovascular events [11].

Hypertension is a chronic condition associated with an

increased risk of cardiovascular mortality and morbidity.

High blood pressure is estimated to lead to over 7 million

deaths each year, about 13% of the total deaths worldwide

[1]. Lowering blood pressure levels in hypertensive

patients has been shown to be a very effective means

of reducing those patients’ cardiovascular risk, with a

significant reduction in cardiovascular morbidity and

mortality [2,3].

The main treatments available for essential hypertension

are blood pressure-lowering drugs and various nondrug

treatment options. Consistently, epidemiological inves-

tigations have found an association between high blood

pressure and different lifestyle factors, high sodium

intake among them [4–7]. This assumption was also

underlined by some recently published systematic

reviews, including randomized controlled trials (RCTs)

showing that salt reduction also lowered blood pressure

[8–10]. In addition, higher salt intake was found to be

National and international professional associations

recommend the consistent, long-term implementation

of nondrug measures in the treatment of essential hyper-

tension. Reduced salt intake is recommended in major

guidelines as one of the first-line interventions in the

treatment of hypertensive patients [12–16].

This investigation is based on a report of the Institute for

Quality and Efficiency in Healthcare in Germany

(IQWiG), which aimed to assess the benefits and harm

of reduced salt intake. This report incorporated existing

systematic reviews. According to the IQWiG methods

[17], such an approach is deemed as resource-saving and

reliable, provided that specific preconditions have been

fulfilled (see below). Such overviews, sometimes called

umbrella reviews or meta-reviews, which combine and

compare different systematic reviews assessing interven-

tions, have recently been adopted by the Cochrane

Collaboration as well [18]. The present publication on

reduced salt intake is part of a package of systematic

DOI:10.1097/HJH.0b013e3283442840

822 Journal of Hypertension 2011, Vol 29 No 5

benefit assessments on different lifestyle interventions.

Results based on previous reports on the effect of weight

reduction have already been published [19–21] and

further reports, for example, on physical activity and

alcohol reduction are in preparation. The present inves-

tigation aimed to review systematically the benefits and

harm of different interventions involving salt reduction

in patients with essential hypertension according to

Preferred Reporting Items for Systematic Reviews and

Meta-Analyses (PRISMA) statement [22].

MethodsEligibility of publicationsThe investigation included systematic reviews of RCTs

of at least 4 weeks’ duration involving nonpregnant

patients aged 18 years or older with essential hyperten-

sion. The intervention to be tested in these trials was a

reduction in salt intake compared to no such reduction in

salt intake or a lower intended salt intake in the inter-

vention group than in the control group. Any additional

(antihypertensive) treatment had to be given equally in

both groups. Excluded were systematic reviews and

health technology assessment (HTA) reports in which

the reduction in salt intake as a primary intervention was

compared to another antihypertensive treatment as a

primary intervention (e.g., reduced salt intake versus diet

or versus blood pressure-lowering drugs).

Outcomes of interestThe evaluation focused on patient-relevant therapy out-

comes (mortality, cardiovascular morbidity and mortality,

hospital stays, terminal renal failure, capacity for work,

health-related quality of life, patient satisfaction, and

adverse events) and blood pressure as a surrogate end-

point in hypertensive people. Patient-relevant therapy

goals and surrogates were prospectively defined in a

protocol and detailed criteria for assessment of the

patient-relevant endpoints were determined in accord-

ance with the IQWiG methods Version 3.0 [17].

Selection of publications and methods of assessmentAs indicated in the Cochrane Handbook [18] and IQWiG

methods Version 3.0 [17], the preparation of a review on

the basis of secondary literature is feasible, if major key

elements are considered as detailed in Table 1 in the

Appendix, http://links.lww.com/HJH/A71.

The bibliographic databases EMBASE and MEDLINE,

and three databases of the Cochrane Library [HTA

Database, The Cochrane Database of Systematic

Reviews (CDSR), Database of Abstracts of Reviews of

Effects (DARE)] were searched for related reviews

published after the year 1997 up to February 2010. All

systematic reviews published in English, German,

French, or Spanish were included. In addition, a primary

literature search update restricted to English and German

publications in EMBASE, MEDLINE/PubMed and

the Cochrane Central Register of Controlled Trials

(CENTRAL) was performed only for the time period

that was not covered by secondary literature. As the last

primary literature search in the systematic reviews was

performed in 2005, we searched for RCTs published

between 2005 and February 2010.

The search strategy is published in detail in the IQWiG

report [23]. Titles and abstracts were screened indepen-

dently by multiple teams of two reviewers (K.H., K.J.,

T.W.G., E.M. and/or A.S.); potentially relevant second-

ary publications were assessed as full texts by the same

reviewers. Differences between reviewers were resolved

by discussion or a third reviewer was involved. The

methodological quality assessment of the relevant

reviews was done according to Oxman and Guyatt’s index

[24,25]. Systematic reviews were included if they scored

at least five out of seven possible points.

Identical inclusion criteria as for the systematic reviews

were used to identify relevant RCTs. The quality assess-

ment of the included RCTs was based on randomization,

blinding, allocation concealment, intention-to-treat

analysis, and further aspects of bias risk, and was con-

ducted independently by K.H. and E.M., who graded the

relevant RCTs as having no (A), moderate (B), or serious

(C) methodological deficiencies.

ResultsResults from the secondary literatureWe identified 1729 potentially relevant publications in

the secondary literature and seven systematic reviews

[8–10,26–29] met the inclusion criteria. All of those were

assessed with at least five out of seven possible points by

the Oxman and Guyatt’s score. These publications were

allocated to four groups of authors and included 62 RCTs

overall (Fig. 1 in the Appendix, http://links.lww.com/

HJH/A71). Table 1 [8–10,28] in the text gives an over-

view of the included systematic reviews. The search

strategies, selection criteria used for inclusion of primary

studies, number and duration of included RCTs, and the

patient characteristics are shown (Table 1 in the text). In

addition, Table 2 of the Appendix, http://links.lww.com/

HJH/A71 provides an outline of the database of relevant

outcomes within the systematic reviews.

Two systematic reviews (Hooper et al. [28] and Dickinson

et al. [8]) aimed for patient-relevant outcomes, but only

Hooper et al. [28] reported relevant patient-related out-

comes such as mortality, cardiovascular events, quality of

life, and adverse events. None of the reviews reported

data on hospital stays, terminal renal failure, capacity for

work, or patient satisfaction (Table 2 in the Appendix,

http://links.lww.com/HJH/A71). Results of the review

published by Hooper et al. [28] are described in the

following: data on all-cause mortality were provided for

three out of eight primary studies. One study reported

four deaths in the intervention and five deaths in the

Benefit assessment of salt reduction in hypertension Matyas et al. 823

Table 1 Characteristics of the systematic reviews/number and duration of the included relevant randomized controlled trials

Systematic review Relevant selection criteria Search

Number/duration(median) ofincluded RCTs

Patientcharacteristics

Dickinson et al. [8]; Sponsoring:National Institute for ClinicalExcellence (NICE)

Inclusion criteria: RCTs;duration �8 weeks; adults;SBP �140 and/or DBP�85 mmHg; exclusion criteria:pregnancy; secondaryhypertension; change inantihypertensive medicationduring follow-up

MEDLINE (1998 to May 2003);EMBASE (1998 to May 2003);CENTRAL (1998 to May 2003);references of hypertensionguidelines, systematic reviewsand meta-analyses (before 1998)

8 RCTs, 8 to52 weeks(52 weeks)

Number of patients:520; mean %female: 24; meanage: 52 years; meanBP: 151/95 mmHg

He and MacGregor [9](Update 2006); Sponsoring:no sponsor

Inclusion criteria: RCTs; duration:�4 weeks; age �18 years;net reduction in 24-h urinarysodium must be equal to orgreater than 40 mmol; exclusioncriteria: pregnancy

MEDLINE (1966 to April 2005);EMBASE (1980 to April 2005);CINHAL (1982 to June 2001);Cochrane Library (up to April2005); references of originalarticles and reviews

20 RCTs, 4 to52 weeks(5 weeks)

Number of patients:802; Median %female: 47 (range:15–76); medianage: 50 years;median BP:149/94 mmHg

Hooper et al. [28]; Sponsoring:NW Research DevelopmentTraining Fellowship

Inclusion criteria: RCTs; duration�26 weeks; age �16 years;exclusion criteria: pregnancy,hospitalized patients

MEDLINE (up to July 2000);EMBASE (up to July 2000);Cochrane Library (up to July2000); CAB abstracts,CVRCT registry, SIGLE (upto May 1998); bibliographiesof identified publicationsand reviews

8 RCTs, 6 monthsto 7 years(12 months)

Number of patients:1188; median %female: 50 (range:0–58); Mean age:n.a.; median BP:145/86 mmHg

Jurgens and Graudal [10];Sponsoring: no sponsor

Inclusion criteria: RCTs, additionalinterventions had to becomparable in the interventiongroups; at least 8 h urinarysodium excretion; age >15 years;exclusion criteria: pregnancy

MEDLINE (1966 to December2001); EMBASE, CCTR(no data of searchtime available)

54 RCTs, 4 to365 days(28 days)

Number of patients:n.a.a; % female: n.a;mean age: 49 years;mean BP: n.a.

BP, blood pressure; n.a., no data available; RCT, randomized controlled trial. a In the meta-analyses, n¼3391 (DBP) and n¼3367 (SBP) were included. These numbersalso include cross-over comparisons and several primary studies <4 weeks of duration.

control group (Morgan et al. [30]), whereas the other two

studies counted no death (Alli et al. [31] and TONE

[32,33]). Cardiovascular events were described in two

(Alli et al. [31] and TONE [32,33]) out of eight studies

and the presented meta-analysis showed no significant

difference between the salt-reduced and control groups

(Hooper et al. [28]). In the review of Hooper et al. [28],

health-related quality of life was described in only one

trial (Thaler et al. [34]). Data were not scaled by a

conventional measurement and it was not possible to

compare the study groups. Adverse events were reported

in two studies within the 2004 review by Hooper et al. In

the study by Thaler et al. [34], muscle cramps were more

frequent in the intervention group. As the difference

between the groups with regard to frequency of muscle

cramps was similar at study entry (29.5% in the inter-

vention group versus 15.3% in the control group), there

was no evidence of an increase in muscle cramps. A

statistically significant smaller number of participants

in the salt-reducing group reported headache in the

TONE trial [32,33], but further details necessary to

interpret this finding were not reported.

For investigations on blood pressure as a surrogate, most

of the analyses showed a blood pressure-lowering effect

in hypertensive patients through reduced salt intake

when compared to a control treatment (Fig. 1 in the text;

Table 3 in the Appendix, http://links.lww.com/HJH/A71).

Over an intervention period of up to 12 months, the

analyses showed a statistically significant difference

with regard to mean SBP reduction ranging from 3.6 to

8.0 mmHg in favor of the intervention groups. For the

same intervention period, a statistically significant differ-

ence with regard to mean DBP reduction ranging from

1.9 to 2.8 mmHg was found in three reviews. In the

fourth publication (Hooper et al. [28]), a more pronounced

reduction was also observed for the intervention (differ-

ence of 4.7 mmHg compared to control treatment),

but this was based on only four trials and without

statistical significance. All data primarily apply to analyses

of patients without concomitant antihypertensive drug

treatment.

In the study by Dickinson et al. [8], results on blood

pressure were based on a meta-analysis of six studies

including 450 untreated patients and showed no hetero-

geneity. There was a statistically significant weighted

mean difference in studies lasting from 8 to 52 weeks in

favor of the salt-reduced group. Including only studies

with a duration of at least 6 months, there was no longer

any statistically significant weighted mean difference.

Similar effects in untreated hypertensive patients favor-

ing the intervention group were obtained in the meta-

analysis lasting between 4 and 52 weeks of follow-up of

824 Journal of Hypertension 2011, Vol 29 No 5

Fig. 1

Systematicreview

Dickinson 20068

He 20049

Hooper 200428

Jürgens 200410

SBP

6

19

4

53

−5.3 (−6.7; −3.9)

−8.0 (−15.8; −0.2)

−4.2 (−5.1; −3.3)

Weighted mean difference (95% CI)[mmHg]

RCTs[n]

DBP

6

20

4

54

−2.5 (−3.2; −1.7)

−2.8 (−3.6; −2.0)

−4.7 (−9.3; 0.04)

−1.9 (−2.5; −1.3)

Weighted mean difference (95% CI)[mmHg]

RCTs[n]

−15 0 15Favours salt reduction Favours control

−15 0 15Favours salt reduction Favours control

−3.6 (−4.6; − 2.5)

Weighted mean differences for SBP and DBP: comparison of the results for the follow-up up to 12 months.

He et al. [9], including 20 comparisons with about 800

patients. There was marked heterogeneity in the blood

pressure results and possible reasons given by the authors

were differences between studies in age, ethnic group,

baseline blood pressure levels, the amount and the

duration of salt intake reduction, and the study quality.

They did not perform further sensitivity analyses due to

the small number of trials and the very limited infor-

mation reported in the studies.

A meta-analysis by Hooper et al. [28] containing four

studies lasting between 6 and 12 months of follow-up

covering 179 hypertensive patients without antihyper-

tensive drug treatment showed a statistically significant

advantage in favor of the intervention group for the SBP

only. There was moderate heterogeneity (P¼ 0.15;

I2¼ 43%). For DBP, there were two studies with the

same follow-up period with 87 untreated hypertensive

Table 2 Characteristics of the randomized controlled trials from prima

RCTRelevant selectioncriteria

Study design/duration of study Interv

He and MacGregor[38]; Sponsoring:UK FoodStandards Agency

Inclusion criteria: age:30–75 years; SBP140–170 or DBP90–105 mmHg; exclusioncriteria: pregnancy, previoustreatment for raised BP;secondary hypertension,previous stroke, ischemicheart disease, heart failure,diabetes mellitus,malignancy or liver disease;women on oral contraceptives

RCT; double-blind;cross-over/6 weeks

2 weonIGtabtab9 p

Meland and Aamland[39]; Sponsoring:Norske HoechstAS, Universityof Bergenstudent grant,Solstrandsfondet

Inclusion criteria: age:20–75 years, patients onantihypertensive drugs;SBP 160–210 and/or DBP90–115 mmHg; exclusioncriteria: drug-inducedhypertension; use ofantihypertensives due toother cardiovascularillnesses

RCT; double-blind;parallel/8 weeks

Salt-groofCG/dato

CG, control group; CI, confidence interval; IG, intervention group; n.a., no data availa

patients that only showed a trend in favor of the inter-

vention group. Hooper et al. identified only one small trial

(Morgan et al. [30,35]) with 62 patients lasting more than a

year in which only the DBP was significantly reduced due

to salt reduction. In addition, Hooper et al. [28] included

three studies with treated hypertensive patients as well,

but the authors did not explain why a meta-analysis was

not performed. One of these trials (TONE [32,33]) did

not report any blood pressure results. In a study by

Morgan and Anderson [36], in which antihypertensive

drug treatment was withdrawn after 3 months in both

groups, after 9 months of follow-up, blood pressure

increased less under salt reduction. In the study by Arroll

and Beaglehole [37], there was a greater mean decrease

after 6 months of intervention for SBP in the salt-reduced

group than in the control group [�9.1 (standard deviation

21.7); �6.2 (standard deviation 21.0) mmHg]. For DBP,

the mean decrease was smaller in the salt-reduced group

ry literature search update

ention Patient characteristics Outcomes

eks run-in phasea reduced-salt diet;

: 9 slow sodiumlets (10 mmol perlet) daily; CG:lacebo tablets daily

No separate analyses forIG and CG available;number of patients:169; % female: n.a.;mean age: 50 years;mean BP:147/91 mmHg

Patient-relevant endpoints:n.a.; surrogate endpoints:duration and extent ofblood pressure changes;BP at study end [meandifference (mmHg]: SBP:�4.8 (95%CI: �6.4 to3.2); P<0.001; DBP:�2.2 (95%CI: �3.1 to�1.4); P<0.001]

reduced diet in bothups; IG: 5 capsules10 mmol sodium/day;: 5 placebo capsulesy (identical capsulesIG)

Number of patientsIG/CG: 57/55;% female: n.a;mean age: IG/CG:57/55 years; meanBP: IG/CG; SBP:157/155 mmHg;DBP 93/92 mmHg

Patient-relevant endpoints:n.a.; surrogate endpoints:duration and extent ofblood pressure changes;BP at study end [meandifference (mmHg): SBP:��5 (95%CI: �11 to 0);P<0.07; DBP: ��5(95% CI: �7 to �1);P<0.02

ble; RCT, randomized controlled trial.

Benefit assessment of salt reduction in hypertension Matyas et al. 825

than in the control group [�1.7 (standard deviation 34.9);

�4.8 (standard deviation 36.1) mmHg].

In the fourth systematic review including 54 studies

(Jurgens and Graudal [10]), no separate analyses for

treated and untreated hypertensive people were per-

formed. For both SBP including 3391 participants in

the analysis and for the DBP including 3367 participants,

there was a significant weighted mean difference in favor

of the intervention group. There was no significant

heterogeneity found for either of the blood pressure

analyses.

Results from randomized controlled trials publishedbetween 2005 and 2010The primary literature search update revealed 573

additional references. Two RCTs [38,39] were included

in this systematic overview. The trial flow is given in

Fig. 2 in the Appendix, http://links.lww.com/HJH/A71.

Table 2 [38,39] in the text provides information on

relevant characteristics of the included RCTs. The qual-

ity assessment of these two studies is presented in

Table 4 in the Appendix, http://links.lww.com/HJH/

A71; one was judged to have moderate and the other

one serious risk of bias.

Both trials lasted only a few weeks and no data on patient-

relevant outcomes were reported. However, blood pres-

sure changes were shown in both studies and indicated a

benefit in the salt-reduced patient groups. The results in

the study by He et al. [38] showed a statistically signi-

ficant difference in SBP and DBP between the inter-

vention and the control groups [SBP: �4.8 mmHg

(95% confidence interval �6.4 to �3.2); P< 0.001;

DBP: �2.2 mmHg (95% confidence interval �3.1 to

�1.4); P< 0.001]. In the study by Meland and Aamland

[39], there was a statistically significant difference

between the groups in favor of the intervention group

only in the DBP [�5 mmHg (95% confidence interval�7

to �1); P< 0.02]. For the SBP, the difference was not

statistically significant [�5 mmHg; (95% confidence

interval �11 to 0); P< 0.07; see Table 2 in the text].

DiscussionBased on high quality secondary literature and an exten-

sive update search for RCTs, we conducted a systematic

overview examining the question of whether salt

reduction in patients with essential hypertension is

beneficial or harmful. The robustness of the results

appears plausible as this overview covers the high quality

evidence available to date, and a primary literature search

update was performed. Within the systematic reviews

included, no primary study was identified in which the

primary objective was to investigate the reduction in salt

intake as an intervention in order to prevent patient-

relevant complications. In relation to blood pressure, all

analyses showed a blood pressure-lowering effect in

hypertensive patients through reduced salt intake when

compared to a control treatment. The reported extent of

the effect size varied among the reviews.

Our findings are not unexpected against the background

of the epidemiological data suggesting that salt intake

is positively associated with blood pressure levels

[11,41–44]. None of the RCTs included in the identified

systematic reviews was powered to detect a potential

benefit indicating that salt-reduced diet decreases unfa-

vorable patient-relevant outcomes. Consequently, evi-

dence for the assumption that salt restriction is associated

with a tremendous reduction in cardiovascular outcomes

as well, is only based on epidemiological observations

[11,41,45]. In the recently published systematic review

and meta-analysis of prospective studies published by

Strazzullo et al. in 2009 [11], including 19 independent

cohort samples with more than 170 000 participants and a

follow-up between 3.5 and 19 years, higher salt intake

was associated with a significantly greater risk of stroke

(pooled relative risk 1.23; 95% confidence interval 1.06–

1.43; P¼ 0.007) and a tendentially higher, though non-

significant, risk of cardiovascular disease was observed

(pooled relative risk 1.14, 95% confidence interval 0.99–

1.32; P¼ 0.07). In a recently published narrative review,

multiple studies have shown that the adjusted relative

risk reduction in controlled observational studies aiming

for reduced sodium intake ranged from 25% over 15 years

to 41% over 3 years [45]. The effect of a direct application

of a salt reduction in daily life has been demonstrated

in an RCT, which investigated the Dietary Approaches

for Stop Hypertension (DASH) diet, rich in fruits and

vegetables and low-fat diary products in combination

with reduced dietary sodium uptake. In patients having

such a diet, it has been shown that the SBP was

11.5 mmHg lower compared to patients with control diet

with high sodium intake [46]. It has been reported that

this blood pressure reduction has been further improved

when patients on the DASH diet additionally exercise

and follow a weight management program [47].

This evidence is further underlined in a long-term obser-

vational follow-up study of two hypertension prevention

trials (TOHP I and II) with prehypertensive patients.

This study does not meet the inclusion criteria of our

review; however, as long-term results are of major

relevance in this context, we would like to discuss them

in further detail. A total of 3126 patients randomly

assigned to salt restriction in TOPH I and TOPH II

were observed for a further 10–15 years after the end of

the original RCTs lasting for 18–48 months. Follow-up

information on cardiovascular outcomes was 77% and for

death 100%, and blinded endpoint evaluation by medical

records was performed. In this long-term observation, the

risk of a cardiovascular event was about 25–30% lower

among those in the salt-reduced group and there was a

trend to a lower mortality rate, which was, however, not

statistically significant [48]. On the basis of those studies,

reduced salt intake is recommended by many leading

826 Journal of Hypertension 2011, Vol 29 No 5

national and international professional associations

[12–16]. There is solid evidence for a health benefit

when blood pressure is reduced to recommended levels,

and in certain patients, lifestyle changes may enable

them to reduce or stop drug therapy as well [32]. In

terms of salt intake, experts in this field advise patients to

first decrease their consumption of processed food, refrain

from adding salt, and eat more fruits and vegetables [49].

Limitations of our overview are that most of the RCTs

included in the systematic reviews provided only a small

number of patients and short follow-up. As a consequence,

none had the power to evaluate patient-relevant outcomes

and no answer can be provided on these aspects. In

addition, the included systematic reviews differ in their

chosen outcomes, inclusion criteria, and search strategies,

which also might cause the differences in the numbers of

studies included in the systematic reviews. Although we

included only high quality systematic reviews, another

limitation is that the reviews might have some flaws that

are passed over to our review as well. Nonetheless, the

results obtained in terms of blood pressure point in the

same direction, which once again further confirms the

assumptions known for a long time that dietary salt restric-

tion appears to be effective with regard to this surrogate.

However, an important limitation is that almost none of the

analyses presented results on patients who were simul-

taneously taking antihypertensive drugs, and an additional

blood pressure-lowering capacity in those patients taking

such medication remains unclear. This needs to be empha-

sized as this raises the question whether the results are

generalizable to patients being treated with antihyper-

tensive drugs. In addition, only one (Hooper et al. [28])

of the four included systematic reviews presented some

limited information on how salt intake was reduced with

the different interventions. This in turn means that no

recommendations can be given on the basis of these results

as to how salt intake should best be reduced. Moreover,

valid long-term data are not available and well founded

information on patient-relevant outcomes does not exist.

The importance of this uncertainty is emphasized by an

example from a study with successful weight reduction.

The Swedish Obese Subject Study (SOS) in which more

than 1700 patients successfully reduced their body weight

by means of bariatric surgery has shown that the initial

postsurgical blood pressure reduction was still present after

2 years, but was almost gone 10 years later [50]. In terms of

adverse events, Klaus et al. [45] gave an overview on

possible risks in terms of a dietary salt reduction,

suggesting that with a modest dietary salt restriction to

5–6 g/day, short episodes of severe diarrhea or longer

episodes of vomiting are not likely to cause sodium

deficiency. Even in geriatric patients and pregnant

women, Klaus et al. [45] deem the benefit as exceeding

potential harm. Drastic salt restrictions to 1 g/day are not

recommended due to pathophysiological considerations

[45].

Since the 1980s, the salt industry has tried to promote

the view that salt reduction provides only a negligible

benefit [41,51], but now, concerted efforts of relevant

working groups and advisory panels throughout the

world and the WHO are exerting pressure on them to

change their strategy [49,52]. These organizations pub-

lish action plans for the implementation of salt-reducing

strategies and give recommendations for a population-

wide salt intake reduction. For example, the WHO has

set out a worldwide target of less than 5 g/day for adults

[49], or a reduction of salt intake by approximately one

half per day assuming that western people consume

about 10 g sodium daily. Though these measures are

all voluntary and not regulated by law, reduction of

sodium in the diet is increasingly becoming a public

health issue. A coronary heart disease model including

the entire US population has recently indicated that

lowering salt intake in the population would in all like-

lihood reduce cardiovascular disease and deaths, and

lower medical costs [53]. Most of the strategies are based

on the United Kingdom Food Standards Agency’s pro-

gram on salt reduction, the Consensus Action on Salt and

Health (CASH) [52]. CASH involves government,

business, and consumer and health groups, based on

the premise that action must address people, environ-

ment, and products. Since CASH was set up in 1996, with

the stepwise and slow reduction of salt content in

primary processed foods bought in supermarkets, public

health campaigns, and a clear labeling, salt intake has

already fallen as documented by a random sample of the

population [40]. Preexisting strategies can now act as a

model for other initiatives in different countries such as

the ‘less salt for all’ task force [54], which is currently

being planned in Germany. After the critical assessment

of risks and benefits of a general restriction of dietary salt

intake, they want to implement short-term, medium-

term and long-term goals. Short and medium goals are to

concentrate on the improvement of the health status of

the population aiming for sodium labeling of food pro-

ducts and the stepwise reduction of salt in processed

food, in fast food chains and restaurants. For long-term

goals, individual patients should be addressed via sus-

tainable health promotion (e.g. advice for nutritional

behavior changes with the focus of promotion in media,

schools, and other education sites). For hypertensive

patients, structured training courses could be a key,

because such training programs with appropriate infor-

mation on nutrition have been successfully imple-

mented to improve patients’ understanding of hyper-

tension and associated complications, thus increasing

adherence with nondrug and drug-based treatments

and improving patient-relevant outcomes [55–59].

Our overview based on secondary and primary literature

published to date proves a blood pressure-lowering effect

when hypertensive patients reduce their salt intake.

However, no valid information was available to show

Benefit assessment of salt reduction in hypertension Matyas et al. 827

conclusively that salt reduction is beneficial or harmful in

terms of patient-relevant outcomes.

AcknowledgementsThe authors thank Siw Waffenschmidt (IQWiG) for

assistance with the literature search strategies, Thomas

Werner Gratzer and Ursula Puringer for support in data

editing, and Eugenia Lamont for final editing of the

article.

E.M., K.J., K.H., T.S., N.P., and A.S. are involved as

external experts in the preparation of rapid reports on

the benefit assessment of nondrug treatment strategies

in patients with essential hypertension for IQWiG, the

German Institute for Quality and Efficiency in Health-

care. L.G.H. is an employee of IQWiG.

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