DIETARY SALT INTAKE: HISTORY, ASSESSMENT, AND BENEFIT IN HYPERTENSIVE TREATMENT

ABSTRACT Multiple lines of investigation including genetic, epidemiological, and interventional studies have demonstrated consistently a positive relationship between salt intake, blood pressure (BP) increment, and cardiovascular consequences. In addition, it has been documented that excessive salt intake can be attributed to various health complications such as asthma, osteoporosis, obesity, and gastric cancer. On the contrary, a reduction in salt intake has been shown to reduce BP and improve health outcomes, although the evidence is not completely unequivocal. Despite this discrepancy, a lowsodium diet is widely being recommended to all hypertensive patients in particular, as evidence against its efficacy in conjunction with optimum hypertensive treatment is well established. Determination of salt intake among hypertensive patients is important since dietary salt restriction hadbeen proven to improve BP control in conjunction with optimum pharmacological management. Various methods have been used to estimate sodium intake includes 24-hrs urinary sodium, overnight urinary sodium, spot urinary sodium/creatinine ratio, and dietary survey methods. Reducingpopulation salt intake has been proven to be beneficial, preventing millions of deaths from cardiovascular disease and stroke, and reducing the burdenon health services. Many individual countries around the globe have already taken action against reducing population salt intake. These strategieswere either led by government, nongovernment organizations, or industry. Keywords: Dietary sodium, Salt, Hypertension, Sodium measurement, Cost-effectiveness.

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Genetically, dietary sodium intake is causally associated with salt-sensitive hypertension risk in a community-based cohort study: a Mendelian randomization approach

European Heart Journal ◽

10.1093/ehjci/ehaa946.2791 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.R Choi

Keyword(s):

Mendelian Randomization ◽

Salt Intake ◽

Sodium Intake ◽

Dietary Sodium ◽

Funding Source ◽

Dietary Salt ◽

Community Based ◽

Dietary Salt Intake ◽

Hypertension Risk ◽

Salt Sensitive Hypertension

Abstract Excessive dietary salt intake is associated with an increased risk of hypertension. Salt sensitivity, i.e., an elevation in blood pressure in response to high dietary salt intake, has been associated with a high risk of cardiovascular disease and mortality. We investigated whether a causal association exists between dietary sodium intake and hypertension risk using Mendelian randomization (MR). We performed an MR study using data from a large genome-wide association study comprising 15,034 Korean adults in a community-based cohort study. A total of 1,282 candidate single nucleotide polymorphisms associated with dietary sodium intake, such as rs2960306, rs4343, and rs1937671, were selected as instrumental variables. The inverse variance weighted method was used to assess the evidence for causality. Higher dietary sodium intake was associated with salt-sensitive hypertension risk. The variants of SLC8E1 rs2241543 and ADD1 rs16843589 were strongly associated with increased blood pressure. In the logistic regression model, after adjusting for age, gender, smoking, drinking, exercise, and body mass index, the GRK4 rs2960306TT genotype was inversely associated with hypertension risk (OR = 0.356, 95% CI = 0.236–0.476). However, the 2350GG genotype (ACE rs4343) exhibited a 2.11-fold increased hypertension risk (OR = 2.114, 95% CI = 2.004–2.224) relative to carriers of the 2350AA genotype, after adjusting for confounders. MR analysis revealed that the odds ratio for hypertension per 1 mg/day increment of dietary sodium intake was 2.24 in participants with the PRKG1 rs12414562 AA genotype. Our findings suggest that dietary sodium intake may be causally associated with hypertension risk. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A3B03034119, 2014M3C9A3064552), and the KRIBB Initiative program. This research was also supported by the Medical Research Center Program (2017R1A5A2015369). This work was supported (in part) by the Yonsei University Research Fund 2017. Bioresources for this study were provided by the National Biobank of Korea and the Centers for Disease Control and Prevention, Republic of Korea (2017-009).

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Renal denervation chronically lowers arterial pressure independent of dietary sodium intake in normal rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01029.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. H2302-H2310 ◽

Cited By ~ 52

Author(s):

Frédéric Jacob ◽

Pilar Ariza ◽

John W. Osborn

Keyword(s):

Arterial Pressure ◽

Salt Intake ◽

Sodium Intake ◽

Recovery Period ◽

Control Period ◽

Dietary Sodium ◽

Renal Nerves ◽

Dietary Salt ◽

Dietary Salt Intake ◽

High Salt Intake

The present study was designed to test the hypothesis that renal nerves chronically modulate arterial pressure (AP) under basal conditions and during changes in dietary salt intake. To test this hypothesis, continuous telemetric recording of AP in intact (sham) and renal denervated (RDNX) Sprague-Dawley rats was performed and the effect of increasing and decreasing dietary salt intake on AP was determined. In protocol 1, 24-h AP, sodium, and water balances were measured in RDNX ( n = 11) and sham ( n = 9) rats during 5 days of normal (0.4% NaCl) and 10 days of high (4.0% NaCl) salt intake, followed by a 3-day recovery period (0.4% NaCl). Protocol 2 was similar with the exception that salt intake was decreased to 0.04% NaCl for 10 days after the 5-day period of normal salt (0.04% NaCl) intake (RDNX; n = 6, sham; n = 5). In protocol 1, AP was lower in RDNX (91 ± 1 mmHg) compared with sham (101 ± 2 mmHg) rats during the 5-day 0.4% NaCl control period. During the 10 days of high salt intake, AP increased <5 mmHg in both groups so that the difference between sham and RDNX rats remained constant. In protocol 2, AP was also lower in RDNX (93 ± 2 mmHg) compared with sham (105 ± 4 mmHg) rats during the 5-day 0.4% NaCl control period, and AP did not change in response to 10 days of a low-salt diet in either group. Overall, there were no between-group differences in sodium or water balance in either protocol. We conclude that renal nerves support basal levels of AP, irrespective of dietary sodium intake in normal rats.

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Immunoreactive Substance P in Human Plasma: Response to Changes in Posture and Sodium Balance

Clinical Science ◽

10.1042/cs0590075 ◽

1980 ◽

Vol 59 (1) ◽

pp. 75-77 ◽

Cited By ~ 6

Author(s):

H. J. Kramer ◽

R. Düsing ◽

H. Stelkens ◽

R. Heinrich ◽

J. Kipnowski ◽

...

Keyword(s):

Substance P ◽

Salt Intake ◽

Sodium Intake ◽

Plasma Concentrations ◽

Mean Value ◽

Dietary Sodium ◽

Sodium Balance ◽

Dietary Salt ◽

Dietary Salt Intake ◽

High Sodium

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 ± 31 pmol/l when subjects were supine and 401 ± 51 pmol/l (P < 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 ± 39 pmol/l at 14.00 hours and a lowest value of 76 ± 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 ± 41 pmol/l, on a sodium intake ad lib., to 244 ± 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 ± 20 pmol/l (P < 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.

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SO035EFFECT OF DIETARY SALT REDUCTION ON BLOOD PRESSURE IN KIDNEY TRANSPLANT PATIENTS: A RANDOMISED CONTROLLED TRIAL

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so035 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Louise Ross ◽

Rebecca Suckling ◽

Fengjun He ◽

Mark Dockrell ◽

Thomas Bailey ◽

...

Keyword(s):

Blood Pressure ◽

Kidney Transplant ◽

Salt Intake ◽

Mean Difference ◽

Urinary Sodium ◽

Dietary Salt ◽

Salt Reduction ◽

Dietary Salt Intake ◽

Transplant Patients ◽

Kidney Transplant Patients

Abstract Background and Aims Cardiovascular morbidity and mortality are increased in kidney transplant patients. High blood pressure (BP) contributes significantly to this risk and is associated with shortened allograft survival. Dietary salt reduction is widely recommended as a strategy to lower BP in the general population and in chronic kidney disease. Due to a lack of evidence there is currently no consensus on dietary salt restriction in kidney transplant patients. The primary aim of the study was to examine the impact of reduced dietary salt intake on BP in kidney transplant patients. Method Sixty stable kidney transplant patients, ≥ 6-months post-transplantation, with BP ≥120/80 mmHg, and sodium intake ≥80 mmol/24hrs, were randomised in this parallel-designed study to receive either a regular-salt diet (target 150 mmol/24hr) or a low-salt diet (target 80 mmol/24hr) for 8-weeks. The primary outcome measure was systolic and diastolic BP. Secondary outcome measures included 24-hour ambulatory BP (ABP) and proteinuria. Dietary salt intake was assessed by 48-hour urinary sodium excretion. Results At baseline, patients (72% men) were 56±11 years with estimated glomerular filtration rate (eGFR) 53±18 mL/min/1.73m2. Mean urinary sodium was 128±42 mmol/24hr, mean systolic BP was 132±12 mmHg, and mean diastolic BP was 77±10 mmHg. At the end of the intervention period sodium excretion was significantly lower in the low-salt group compared with the regular-salt group (90±37 vs. 132±51 mmol/24hr; adjusted mean difference, -36 [95% CI, -59 to -14] mmol/24hr; P=0.002). We found no difference in systolic BP (adjusted mean difference, -2 [95% CI, -12 to 9] mmHg; P=0.750), diastolic BP (adjusted mean difference, 0 [95% CI, -4 to 4] mmHg; P=0.887), 24-hour systolic ABP (adjusted mean difference, -3 [95% CI, -9 to 2] mmHg; P=0.213) or 24-hour diastolic ABP (adjusted mean difference, -2 [95% CI, -5 to 1] mmHg; P=0.267). There was no significant effect on proteinuria or eGFR. Conclusion In this study baseline urinary sodium was lower than expected and baseline BP was well controlled. Reducing dietary salt by 2g/day did not have a significant effect on office blood pressure readings.

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Clearance of endogenous lithium in humans: altered dietary salt intake and comparison with exogenous lithium clearance

AJP Renal Physiology ◽

10.1152/ajprenal.1995.268.4.f718 ◽

1995 ◽

Vol 268 (4) ◽

pp. F718-F722 ◽

Cited By ~ 3

Author(s):

E. Folkerd ◽

D. R. Singer ◽

F. P. Cappuccio ◽

N. D. Markandu ◽

B. Sampson ◽

...

Keyword(s):

Salt Intake ◽

Sodium Intake ◽

Lithium Concentration ◽

Fractional Excretion ◽

Dietary Sodium ◽

Lithium Clearance ◽

Dietary Salt ◽

Renal Handling ◽

Dietary Salt Intake ◽

High Sodium

We compared endogenous with exogenous lithium clearance (CLi) and studied the effects of dietary salt intake on endogenous CLi in healthy volunteers. Lithium was detectable within a narrow fourfold range in serum and in urine in all 25 subjects studied [serum (n = 25), mean 0.27 +/- 0.02 mumol/l, range 0.13-0.55 mumol/l; urine (n = 20), range 1.49–7.32, mean 4.09 +/- 0.36 mumol/24 h]. Mean clearance and fractional excretion of endogenous lithium were lower (15.2 +/- 2.0 ml/min and 16.4 +/- 2.1%, respectively) compared with results obtained using the exogenous CLi technique (25.5 +/- 1.7 ml/min and 27.9 +/- 2.1%; P < 0.01 and P < 0.05, respectively; n = 17). In a separate group of six normal subjects, absolute (8.7 +/- 2.9 vs. 20.7 +/- 3.8 ml/min) and fractional excretion of lithium (8.3 +/- 2.9 vs. 18.0 +/- 5.1%) were significantly lower on 5 days of low (31 +/- 10 mmol/day) vs. high sodium intake (357 +/- 78 mmol/day; P < 0.05). Use of endogenous CLi precludes the need for lithium tablets. This could be a particular advantage in population studies and permits serial measurement of CLi on different days. Our results show that it is important to take dietary sodium intake into account in studies of endogenous CLi. Lower values for endogenous compared with exogenous CLi could reflect differences in renal handling depending on the plasma lithium concentration. This clearly requires further study.

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Dietary salt enhances benzamil-sensitive component of myogenic constriction in mesenteric arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00571.2007 ◽

2008 ◽

Vol 294 (1) ◽

pp. H409-H420 ◽

Cited By ~ 24

Author(s):

Nikki L. Jernigan ◽

Babette LaMarca ◽

Josh Speed ◽

Lauren Galmiche ◽

Joey P. Granger ◽

...

Keyword(s):

Vascular Reactivity ◽

Salt Intake ◽

Mesenteric Arteries ◽

Dietary Sodium ◽

Epithelial Tissue ◽

Sprague Dawley ◽

Resistance Arteries ◽

Dietary Salt ◽

Dietary Salt Intake ◽

And Function

Recent work from our laboratory indicates that epithelial Na+ channel (ENaC) function plays an important role in modulating myogenic vascular reactivity. Increases in dietary sodium are known to affect vascular reactivity. Although previous studies have demonstrated that dietary salt intake regulates ENaC expression and activity in epithelial tissue, the importance of dietary salt on ENaC expression in vascular smooth muscle cells (VSMCs) and its role in myogenic constriction is unknown. Therefore, the goal of the present study was to determine whether dietary salt modulates ENaC expression and function in myogenic vasoconstriction. To accomplish this goal, we examined ENaC expression in freshly dispersed VSMCs and pressure-induced vasoconstrictor responses in isolated mesenteric resistance arteries from normotensive Sprague-Dawley rats fed a normal-salt (NS; 0.4% NaCl) or high-salt (HS; 8% NaCl for 2 wk) diet. VSMCs from the mesenteric arteries of NS-fed animals express α-, β-, and γ-ENaC. The HS diet reduced whole cell α- and γ-ENaC and induced a pronounced translocation of β-ENaC from intracellular regions toward the VSMC membrane (∼336 nm). Associated with this change in expression was a change in the importance of ENaC in pressure-induced constriction. Pressure-induced constriction in NS-fed animals was insensitive to ENaC inhibition with 1 μM benzamil, suggesting that ENaC proteins do not contribute to myogenic constriction in mesenteric arteries under NS intake. In contrast, ENaC inhibition blocked pressure-induced constriction in HS-fed animals. These data suggest that dietary sodium regulates ENaC expression and the quantitative importance of the vascular ENaC signaling pathway contributing to myogenic constriction.

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Relationship between urinary sodium excretion and serum aldosterone in patients with diabetes in the presence and absence of modifiers of the renin–angiotensin–aldosterone system

Clinical Science ◽

10.1042/cs20130128 ◽

2013 ◽

Vol 126 (2) ◽

pp. 147-154 ◽

Cited By ~ 8

Author(s):

Renata Libianto ◽

George Jerums ◽

Que Lam ◽

Angela Chen ◽

Sara Baqar ◽

...

Keyword(s):

Sodium Excretion ◽

Salt Intake ◽

Urinary Sodium Excretion ◽

Urinary Sodium ◽

Dietary Salt ◽

Renin Angiotensin Aldosterone System ◽

Dietary Salt Intake ◽

Serum Aldosterone ◽

Patients With Diabetes ◽

The Relationship

Although low dietary salt intake has beneficial effects on BP (blood pressure), low 24hUNa (24 h urinary sodium excretion), the most accurate estimate of dietary salt intake, is associated with increased mortality in people with diabetes. In the non-diabetic population, low salt intake is associated with increased RAAS (renin–angiotensin–aldosterone system) activity. In this cross-sectional study, we examined the relationship between 24hUNa, PRA (plasma renin activity), serum aldosterone and BNP (brain natriuretic peptide) in patients with diabetes. Clinical characteristics, 24hUNa, PRA, serum aldosterone and BNP were recorded in 222 consecutive patients (77% with Type 2 diabetes) attending a diabetes clinic at a tertiary hospital. The relationship between 24hUNa, serum aldosterone, PRA, BNP, urinary potassium excretion, serum potassium, serum sodium, eGFR (estimated glomerular filtration rate), urinary albumin excretion and HbA1c (glycated haemoglobin) was examined by a multivariable regression model. Levels of 24hUNa significantly predicted serum aldosterone in a linear fashion (R2=0.20, P=0.002). In the subgroup of patients (n=46) not taking RAAS-modifying agents, this relationship was also observed (R2=0.10, P=0.03), and the effect of 24hUNa on serum aldosterone was found to be more pronounced than in the whole cohort (coefficient=−0.0014, compared with −0.0008). There was no demonstrable relationship between 24hUNa and PRA or BNP. Low 24hUNa is associated with increased serum aldosterone in people with diabetes, in the presence and absence of RAAS-modifying agents. This raises the possibility that stimulation of the RAAS may be a mechanism that contributes to adverse outcomes observed in patients with low 24hUNa.

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Effects of changes in dietary sodium intake on aortic sodium pump activity in the rat

Clinical Science ◽

10.1042/cs0720143 ◽

1987 ◽

Vol 72 (1) ◽

pp. 143-146 ◽

Cited By ~ 4

Author(s):

Richard Bradlaugh ◽

Robert F. Bing ◽

John D. Swales ◽

Herbert Thurston

Keyword(s):

Smooth Muscle ◽

Sodium Pump ◽

Salt Intake ◽

Sodium Intake ◽

Dietary Sodium ◽

Dietary Salt ◽

Salt Loading ◽

Sodium Efflux ◽

Salt Restriction ◽

Dietary Salt Intake

1. Aortic smooth muscle sodium efflux was studied in normal rats undergoing salt restriction or salt loading. 2. Sodium efflux rate constant was not changed by salt loading but fell significantly with salt restriction. This change was not associated with a fall in blood pressure. 3. These studies show that smooth muscle sodium transport can be influenced by dietary salt intake but do not support the concept that salt loading leads to the inhibition of the vascular smooth muscle sodium pump.

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Effect of Salt Intake on the Serum Cardiotrophin-1 Levels in Chinese Adults

Annals of Nutrition and Metabolism ◽

10.1159/000494436 ◽

2018 ◽

Vol 73 (4) ◽

pp. 302-309 ◽

Cited By ~ 1

Author(s):

Keke Wang ◽

Chao Chu ◽

Jiawen Hu ◽

Yang Wang ◽

Wenling Zheng ◽

...

Keyword(s):

Vascular Function ◽

Salt Intake ◽

Northern China ◽

Baseline Period ◽

Dietary Sodium ◽

Dietary Salt ◽

Chinese Adults ◽

Dietary Salt Intake ◽

Low Salt ◽

The Mean

Background: Dietary sodium affects fluctuations in blood pressure (BP) and vascular function. Cardiotrophin-1 (CT-1), a stress-induced cytokine that belongs to the interleukin 6 family, is released by cells in response to potentially harmful stresses and plays a pivotal role in congestive heart failure, hypertension and arterial stiffness. In this study, we performed a randomized trial to confirm the effects of altered salt intake on the serum CT-1 levels in humans. Methods: Forty-four subjects (18–65 years of age) were selected from a rural community in northern China. All subjects initially maintained a baseline period for 3 days, transitioned to a low-salt (LS) diet for 7 days (3.0 g/day of NaCl) and then a high-salt (HS) diet for an additional 7 days (18.0 g/day of NaCl). Results: For the whole group, the serum CT-1 concentrations were significantly increased in the HS period compared to those of the LS period (293.50 ± 137.70 vs. 360.40 ± 162.83 pg/mL, p = 0.040). The serum CT-1 concentrations significantly decreased from the baseline period to the LS diet (419.91 ± 123.50 to 256.49 ± 109.75 pg/mL, p < 0.01) and significantly increased from the LS to HS diet (256.49 ± 109.75 to 414.39 ± 191.21 pg/mL, p < 0.01). These changes were observed in salt-sensitive (SS) individuals but not in salt-resistant (SR) individuals. In addition, a significant positive relationship was observed between the changes in the CT-1 concentrations and systolic BP as well as the changes in the mean arterial pressure from the LS period to the HS period (r = 0.376, p = 0.012; r = 0.311, p = 0.040). The serum CT-1 concentrations were positively correlated with the 24-h urinary sodium-to-potassium (Na/K) excretion ratios during both of the LS and HS diet intervention periods in SS subjects (r = 0.621, p < 0.01), but this correlation was not evident in SR subjects (r = 0.208, p = 0.107). Conclusions: Our study indicates that variations in dietary salt intake affect the serum CT-1 levels in Chinese adults.

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Assessment of Dietary Sodium Intake Using the Scored Salt Questionnaire in Autosomal Dominant Polycystic Kidney Disease

Nutrients ◽

10.3390/nu12113376 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3376

Author(s):

Annette T. Y. Wong ◽

Alexandra Munt ◽

Margaret Allman-Farinelli ◽

Sunil V. Badve ◽

Neil Boudville ◽

...

Keyword(s):

Sodium Excretion ◽

Autosomal Dominant ◽

Salt Intake ◽

Sodium Intake ◽

Dietary Sodium ◽

Dietary Salt ◽

Polycystic Kidney ◽

Urine Sodium ◽

Dietary Salt Intake ◽

Autosomal Dominant Polycystic Kidney

The excess intake of dietary sodium is a key modifiable factor for reducing disease progression in autosomal dominant polycystic kidney disease (ADPKD). The aim of this study was to test the hypothesis that the scored salt questionnaire (SSQ; a frequency questionnaire of nine sodium-rich food types) is a valid instrument to identify high dietary salt intake in ADPKD. The performance of the SSQ was evaluated in adults with ADPKD with an estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 during the screening visit of the PREVENT-ADPKD trial. High dietary sodium intake (HSI) was defined by a mean 24-h urinary sodium excretion ≥ 100 mmol/day from two collections. The median 24-h urine sodium excretion was 132 mmol/day (IQR: 112–172 mmol/d) (n = 75; mean age: 44.6 ± 11.5 years old; 53% female), and HSI (86.7% of total) was associated with male gender and higher BMI and systolic blood pressure (p < 0.05). The SSQ score (73 ± 23; mean ± SD) was weakly correlated with log10 24-h urine sodium excretion (r = 0.29, p = 0.01). Receiving operating characteristic analysis showed that the optimal cut-off point in predicting HSI was an SSQ score of 74 (area under the curve 0.79; sensitivity 61.5%; specificity 90.0%; p < 0.01). The evaluation of the SSQ in participants with a BMI ≥ 25 (n = 46) improved the sensitivity (100%) and the specificity (100%). Consumers with an SSQ score ≥ 74 (n = 41) had higher relative percentage intake of processed meats/seafood and flavourings added to cooking (p < 0.05). In conclusion, the SSQ is a valid tool for identifying high dietary salt intake in ADPKD but its value proposition (over 24-h urinary sodium measurement) is that it may provide consumers and their healthcare providers with insight into the potential origin of sodium-rich food sources.

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