A few more on the problems with salt...
1) Salt & healtha) Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ. 2013 Apr 3;346:f1326. doi: 10.1136/bmj.f1326.
PMID: 23558163
Free Article
http://www.bmj.com/content/346/bmj.f132 ... d=23558163Abstract
OBJECTIVE: To assess the effect of decreased sodium intake on blood pressure, related cardiovascular diseases, and potential adverse effects such as changes in blood lipids, catecholamine levels, and renal function.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, the Latin American and Caribbean health science literature database, and the reference lists of previous reviews.
STUDY SELECTION: Randomised controlled trials and prospective cohort studies in non-acutely ill adults and children assessing the relations between sodium intake and blood pressure, renal function, blood lipids, and catecholamine levels, and in non-acutely ill adults all cause mortality, cardiovascular disease, stroke, and coronary heart disease. STUDY APPRAISAL AND SYNTHESIS: Potential studies were screened independently and in duplicate and study characteristics and outcomes extracted. When possible we conducted a meta-analysis to estimate the effect of lower sodium intake using the inverse variance method and a random effects model. We present results as mean differences or risk ratios, with 95% confidence intervals.
RESULTS: We included 14 cohort studies and five randomised controlled trials reporting all cause mortality, cardiovascular disease, stroke, or coronary heart disease; and 37 randomised controlled trials measuring blood pressure, renal function, blood lipids, and catecholamine levels in adults. Nine controlled trials and one cohort study in children reporting on blood pressure were also included. In adults a reduction in sodium intake significantly reduced resting systolic blood pressure by 3.39 mm Hg (95% confidence interval 2.46 to 4.31) and resting diastolic blood pressure by 1.54 mm Hg (0.98 to 2.11). When sodium intake was <2 g/day versus =/>2 g/day, systolic blood pressure was reduced by 3.47 mm Hg (0.76 to 6.18) and diastolic blood pressure by 1.81 mm Hg (0.54 to 3.08). Decreased sodium intake had no significant adverse effect on blood lipids, catecholamine levels, or renal function in adults (P>0.05). There were insufficient randomised controlled trials to assess the effects of reduced sodium intake on mortality and morbidity. The associations in cohort studies between sodium intake and all cause mortality, incident fatal and non-fatal cardiovascular disease, and coronary heart disease were non-significant (P>0.05). Increased sodium intake was associated with an increased risk of stroke (risk ratio 1.24, 95% confidence interval 1.08 to 1.43), stroke mortality (1.63, 1.27 to 2.10), and coronary heart disease mortality (1.32, 1.13 to 1.53). In children, a reduction in sodium intake significantly reduced systolic blood pressure by 0.84 mm Hg (0.25 to 1.43) and diastolic blood pressure by 0.87 mm Hg (0.14 to 1.60).
CONCLUSIONS:
High quality evidence in non-acutely ill adults shows that reduced sodium intake reduces blood pressure and has no adverse effect on blood lipids, catecholamine levels, or renal function, and moderate quality evidence in children shows that a reduction in sodium intake reduces blood pressure. Lower sodium intake is also associated with a reduced risk of stroke and fatal coronary heart disease in adults.
The totality of evidence suggests that most people will likely benefit from reducing sodium intake.b) Salt in health and disease--a delicate balance.
N Engl J Med. 2013 Mar 28;368(13):1229-37. doi: 10.1056/NEJMra1212606.
CONCLUSIONS
Although it has been difficult to separate salt need from salt preference, current levels of salt consumption exceed salt need and are associated with adverse clinical outcomes. High salt intake is associated with high blood pressure and increased rates of cardiovascular disease. Experimental studies continue to provide information about mechanisms for these adverse effects of salt. In clinical trials, a reduction in salt intake is associated with reduced blood pressure, more so in persons with hypertension than in those with normal blood pressure. Although not discussed in the present review, it should be noted that reduced salt intake is associated with greater blood-pressure responses to antihypertensive drug therapy, including drug therapy in patients with resistant hypertension.85,86 Most, but not all, clinical trials have shown that reduced salt intake is also associated with decreased risks of cardiovascular events and death. Consequently, recommendations for reducing the currently high levels of salt consumption in the general population seem justifiable, although in terms of safety, the lower limit of salt consumption has not been clearly identified. It may be premature to dis-count the apparently paradoxical cardiovascular outcomes associated with low salt intake, particularly in specific clinical conditions (e.g., type 1 or type 2 diabetes and congestive heart failure that is aggressively treated with diuretic agents). Less-rigorous targets for salt reduction may be appropriate for these and other patient groups.
2) Salt impairs the endotheliuma) Effects of a low-salt diet on flow-mediated dilatation in humans. Am J Clin Nutr. 2009 Feb;89(2):485-90. doi: 10.3945/ajcn.2008.26856. Epub 2008 Dec 23. PMID:19106240
Abstract
BACKGROUND:
The effect of salt reduction on vascular function, assessed by brachial artery flow-mediated dilatation (FMD), is unknown.
OBJECTIVE:
Our aim was to compare the effects of a low-salt (LS; 50 mmol Na/d) diet with those of a usual-salt (US; 150 mmol Na/d) diet on FMD.
DESIGN:
This was a randomized crossover design in which 29 overweight and obese normotensive men and women followed an LS diet and a US diet for 2 wk. Both diets had similar potassium and saturated fat contents and were designed to ensure weight stability. After each intervention, FMD, pulse wave velocity, augmentation index, and blood pressure were measured.
RESULTS:
FMD was significantly greater (P = 0.001) with the LS diet (4.89 +/- 2.42%) than with the US diet (3.37 +/- 2.10%), systolic blood pressure was significantly (P = 0.02) lower with the LS diet (112 +/- 11 mm Hg) than with the US diet (117 +/- 13 mm Hg), and 24-h sodium excretion was significantly lower (P = 0.0001) with the LS diet (64.1 +/- 41.3 mmol) than with the US diet (156.3 +/- 56.7 mmol). There was no correlation between change in FMD and change in 24-h sodium excretion or change in blood pressure. No significant changes in augmentation index or pulse wave velocity were observed.
CONCLUSIONS:
Salt reduction improves endothelium-dependant vasodilation in normotensive subjects independently of the changes in measured resting clinic blood pressure. These findings suggest additional cardioprotective effects of salt reduction beyond blood pressure reduction. The trial is registered with the Australian and New Zealand Clinical Trials Registry (unique identifier: ANZCTR12607000381482;
http://www.anzctr.org.au/trial_view.aspx?ID=82159).
b) Low dietary sodium intake is associated with enhanced vascular endothelial function in middle-aged and older adults with elevated systolic blood pressure. Ther Adv Cardiovasc Dis. 2009 Oct;3(5):347-56. doi: 10.1177/1753944709345790. Epub 2009 Sep 1.
Abstract
BACKGROUND: Age and increasing systolic blood pressure (BP) are associated with vascular endothelial dysfunction, but the factors involved are incompletely understood. We tested the hypothesis that vascular endothelial function is related to dietary sodium intake among middle-aged and older adults (MA and O) with elevated systolic BP.
METHODS: Data were analyzed on 25 otherwise healthy adults aged 48-73 years with high normal systolic BP or stage I systolic hypertension (130-159 mmHg). Self-reported sodium intake was <100 mmol/d in 12 (7 M) subjects (low sodium, 73+/-6 mmol/d) and between 100 and 200 mmol/d in 13 (9 M) subjects (normal sodium, 144+/-6 mmol/d).
RESULTS: Groups did not differ in other dietary factors, age, body weight and composition, BP, metabolic risk factors, physical activity and maximal aerobic capacity. Plasma concentrations of norepinephrine, endothelin-1, oxidized low-density lipoproteins (LDL), antioxidant status and inflammatory markers did not differ between groups. Brachial artery flow-mediated dilation (FMD) was 42% (mm Delta) to 52% (% Delta) higher in the low versus normal sodium group (p < 0.05). In all subjects, brachial artery FMD was inversely related to dietary sodium intake (FMD mm Delta r =-0.40, p < 0.05; %Delta r =-0.53, p < 0.01). Brachial artery FMD was not related to any other variable. In contrast, endothelium-independent dilation did not differ between groups (p >or= 0.24) and was not related to sodium intake in the overall group (p >or= 0.29).
CONCLUSIONS: Low sodium intake is associated with enhanced brachial artery FMD in MA and O with elevated systolic BP. These results suggest that dietary sodium restriction may be an effective intervention for improving vascular endothelial function in this high-risk group.
c) Endothelial function is impaired after a high-salt meal in healthy subjects. Am J Clin Nutr. 2011 Mar;93(3):500-5. doi: 10.3945/ajcn.110.006155. Epub 2011 Jan 12. PMID: 21228265
Abstract
BACKGROUND:
Dietary salt is related to blood pressure (BP), and cardiovascular disease and increased sodium intakes have been shown to impair vascular function. The effect of salt on endothelial function postprandially is unknown.
OBJECTIVE:
The aim was to investigate the postprandial effect of dietary salt on endothelial function as measured by flow-mediated dilatation (FMD) and peripheral arterial tonometry in healthy subjects.
DESIGN:
Sixteen healthy, normotensive subjects received a meal with added salt (HSM; 65 mmol Na) and a control low-salt meal (LSM; 5 mmol Na) on 2 separate occasions in a randomized order. Endothelial function was measured while fasting and postprandially at 30, 60, 90, and 120 min by using FMD and reactive hyperemia peripheral arterial tonometry. BP was also measured.
RESULTS:
Baseline FMD, reactive hyperemia index (RHI), and BP values were similar across interventions. Overall FMD was reduced 2 h postprandially. FMD was significantly more impaired after the HSM than after the LSM at 30 min [HSM (mean ± SD): 3.39 ± 2.44%; LSM: 6.05 ± 3.21%; P < 0.01] and at 60 min (HSM: 2.20 ± 2.77%; LSM: 4.64 ± 2.48%; P < 0.01). No significant differences in BP or RHI were observed between meals.
CONCLUSIONS:
An HSM, which reflects the typical amount of salt consumed in a commonly eaten meal, can significantly suppress brachial artery FMD within 30 min. These results suggest that high salt intakes have acute adverse effects on vascular dilatation in the postprandial state. This trial was registered at
http://www.anzctr.org.au/trial_view.aspx?ID=335115 as ACTRN12610000124033.
d) High dietary sodium intake impairs endothelium-dependent dilation in healthy salt-resistant humans. J Hypertens. 2012 Dec 20. [Epub ahead of print] PMID:23263240. J Hypertens. 2013 Mar;31(3):530-6. doi: 10.1097/HJH.0b013e32835c6ca8. PMID 23263240
Abstract
BACKGROUND:: Excess dietary sodium has been linked to the development of hypertension and other cardiovascular diseases. In humans, the effects of sodium consumption on endothelial function have not been separated from the effects on blood pressure. The present study was designed to determine if dietary sodium intake affected endothelium-dependent dilation (EDD) independently of changes in blood pressure.
METHOD:: Fourteen healthy salt-resistant adults were studied (9M, 5F; age 33 ± 2.4 years) in a controlled feeding study. After a baseline run-in diet, participants were randomized to a 7-day high-sodium (300-350 mmol/day) and 7-day low-sodium (20 mmol/day) diet. Salt resistance, defined as a 5 mmHg or less change in a 24-h mean arterial pressure, was individually assessed while on the low-sodium and high-sodium diets and confirmed in the participants undergoing study (low-sodium: 85 ± 1 mmHg; high-sodium: 85 ± 2 mmHg). EDD was determined in each participant via brachial artery flow-mediated dilation on the last day of each diet.
RESULTS:: Sodium excretion increased during the high-sodium diet (P < 0.01). EDD was reduced on the high-sodium diet (low: 10.3 ± 0.9%, high: 7.3 ± 0.7%; P < 0.05). The high-sodium diet significantly suppressed plasma renin activity (PRA), plasma angiotensin II, and aldosterone (P < 0.05).
CONCLUSION:: These data demonstrate that excess salt intake in humans impairs endothelium-dependent dilation independently of changes in blood pressure.
e) Dietary sodium restriction reverses vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure. J Am Coll Cardiol. 2013 Jan 22;61(3):335-43. doi: 10.1016/j.jacc.2012.09.010. Epub 2012 Nov 7. PMID 23141486
Abstract
OBJECTIVES: This study sought to determine the efficacy of dietary sodium restriction (DSR) for improving vascular endothelial dysfunction in middle-aged/older adults with moderately elevated systolic blood pressure (SBP) (130-159 mm Hg) and the associated physiological mechanisms.
BACKGROUND: Vascular endothelial dysfunction develops with advancing age and elevated SBP, contributing to increased cardiovascular risk. DSR lowers BP, but its effect on vascular endothelial function and mechanisms involved are unknown.
METHODS: Seventeen subjects (11 men and 6 women; mean age, 62 ± 7 years) completed a, randomized crossover study of 4 weeks of both low (DSR) and normal sodium intake. Vascular endothelial function (endothelium-dependent dilation; EDD), nitric oxide (NO)/tetrahydrobiopterin (BH(4)) bioavailability, and oxidative stress-associated mechanisms were assessed following each condition.
RESULTS: Urinary sodium excretion was reduced by ≈ 50% (to 70 ± 30 mmol/day), and conduit (brachial artery flow-mediated dilation [FMD(BA)]) and resistance (forearm blood flow responses to acetylcholine [FBF(ACh)]) artery EDD were 68% and 42% (peak FBF(ACh)) higher following DSR (p < 0.005). Low sodium markedly enhanced NO-mediated EDD (greater ΔFBF(ACh) with endothelial NO synthase inhibition) without changing endothelial NO synthase expression/activation (Ser 1177 phosphorylation), restored BH(4) bioactivity (less ΔFMD(BA) with acute BH(4)), abolished tonic superoxide suppression of EDD (less ΔFMD(BA) and ΔFBF(ACh) with ascorbic acid infusion), and increased circulating superoxide dismutase activity (all p < 0.05). These effects were independent of ΔSBP. Other subject characteristics/dietary factors and endothelium-independent dilation were unchanged.
CONCLUSIONS: DSR largely reversed both macro- and microvascular endothelial dysfunction by enhancing NO and BH(4) bioavailability and reducing oxidative stress. Our findings support the emerging concept that DSR induces "vascular protection" beyond that attributable to its BP-lowering effects.
3) Salt & blood pressurea) Long-term effects of salt substitution on blood pressure in a rural North Chinese population. J Hum Hypertens. 2012 Dec 20. doi: 10.1038/jhh.2012.63. [Epub ahead of print] PMID:23254595
Abstract
Dietary sodium and potassium intake can influence blood pressure. The effects of salt substitution on patients with hypertension and normotensive family member controls, however, have not been evaluated in a rural Chinese population.
The objective of this study, accordingly, was to assess the long-term effects of salt substitution on blood pressure.
We conducted a double-blind, randomized controlled trial among 200 families in rural China to establish the 2-year effects of a reduced-sodium, high-potassium salt substitute (65% sodium chloride, 25% potassium chloride, 10% magnesium sulfate) compared with normal salt (100% sodium chloride) on blood pressure.
Of the 462 individuals in the trial, 372 completed the study (81%). For normotensive subjects, the mean overall difference in systolic and diastolic blood pressure between the two groups at the 24-month follow-up was 2 mm Hg (95% confidence interval (CI) 0-4 mm Hg, P<0.05) and 2 mm Hg (95% CI 1-3 mm Hg, P<0.05), respectively. For subjects with hypertension, the mean overall decrease in systolic blood pressure showed a 4-mm Hg (95% CI 2-6 mm Hg, P<0.05) decrease between the two groups. Diastolic blood pressure was not affected by salt use in the hypertensive group.
Salt substitution lowers systolic blood pressure in hypertensive patients and lowers both systolic and diastolic blood pressure in normotensive controls. Salt substitution, therefore, may be an effective adjuvant therapy for hypertensive patients and the potential efficacy in preventing hypertension in normotensive individuals.4) Salt now linked to auto-immune diseasea) Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1.Nature. 2013 Apr 25;496(7446):513-7. doi: 10.1038/nature11984. Epub 2013 Mar 6.
http://www.ncbi.nlm.nih.gov/pubmed/23467085b) Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells. Nature. 2013 Apr 25;496(7446):518-22. doi: 10.1038/nature11868. Epub 2013 Mar 6.
http://www.ncbi.nlm.nih.gov/pubmed/23467095c) Immunology Exacerbating Autoimmune Disease with Salt
Sci. Signal., 30 April 2013 Vol. 6, Issue 273, p. ec97
[DOI: 10.1126/scisignal.2004284]
EDITORS' CHOICE
http://stke.sciencemag.org/cgi/content/ ... a051ac6c83d) Science Volume 339, Number 6124, Issue of 8 March 2013
Dietary Salt Linked to Autoimmune Diseases
http://news.sciencemag.org/sciencenow/2 ... iseas.htmlSalt in food may increase the risk of autoimmune diseases, according to provocative results reported this week in Nature. Immunobiologist David Hafler of the Yale School of Medicine and colleagues determined that a pinch of salt triggered cultures of unspecialized T cells to produce large numbers of destructive TH17 cells, which have been implicated in diseases such as psoriasis, rheumatoid arthritis, and multiple sclerosis. They also showed that a salt-rich diet makes mice more susceptible to experimental autoimmune encephalomyelitis (EAE), a rodent illness similar to multiple sclerosis.
A salt connection also crystallized when computational biologist Aviv Regev of the Broad Institute in Cambridge, immunologist Vijay Kuchroo of Harvard Medical School in Boston, and colleagues pieced together the molecular circuit that controls specialization of TH17 cells. An influential gene was SGK1, which helps cells manage sodium levels. And mice on high-salt rations developed a milder form of EAE if they lacked SGK1. The work doesn't establish that salt drives human autoimmune diseases, but "the stage is set to do precise experiments to test the hypothesis," Kuchroo says.
5) Salt & Strokea) The mediating effect of the Mediterranean diet on the role of discretionary and hidden salt intake regarding non-fatal acute coronary syndrome or stroke events: case/case-control study.
Atherosclerosis.
2012 Nov;225(1):187-93.
doi: 10.1016/j.atherosclerosis.2012.08.004. Epub 2012 Aug 27.
Abstract
OBJECTIVES: The aim of the present work was to evaluate the association between salt and salty food consumption on the development of an acute coronary syndrome (ACS) or ischemic stroke, under the context of adherence to the Mediterranean diet.
METHODS: During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke and 500 population-based, control subjects, one-for-one matched to the patients by age and sex. Socio-demographic, clinical, psychological, dietary and other lifestyle characteristics were measured. Consumption of foods with high salt concentration was evaluated with a special score (range 0-10). Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range: 0-55).
RESULTS: After adjustment for potential confounding factors,
use of salt added in table was associated with 81% higher likelihood of stroke (95% Confidence Interval: 1.03-3.20), whereas no association was observed regarding the development of ACS. Salt use during cooking was not associated with the development of ACS or stroke.
Each unit increase of the score evaluating total salty food consumption was associated with 33% higher likelihood of stroke development (95% Confidence Interval: 1.08-1.64), but not with ACS. The effect of salt and salty food consumption regarding stroke presence was more evident for participants with lower adherence to the Mediterranean diet.
CONCLUSION: Simple dietary changes, with emphasis on reducing salt and salty food consumption, along with better adherence to the Mediterranean diet, should be incorporated in public health strategies for the primary prevention of stroke.
PMID: 22975231
b) High salt intake and stroke:
meta-analysis of the epidemiologic evidence.
CNS Neurosci Ther. 2012 Aug;18(8):691-701.
doi: 10.1111/j.1755-5949.2012.00355.x. Epub 2012 Jun 28.
Abstract
Research on the potential impact of high salt intake on health has grown rapidly over the last decades. Recent studies have suggested that high salt intake could also be associated with adverse effects on cardiovascular system. The review evaluated the current level of epidemiologic evidence on the association between the level of habitual salt intake and stroke outcome. We also suggest further research direction. There were 21 independent samples from 12 studies, with 225,693 participants (follow-up, 3-19 years) and 8135 stroke events. High salt intake was associated with risk of stroke event (pooled odd ratio [OR], 1.34; 95% confidence interval [CI], 1.19-1.51), stroke death (1.40; 1.21-1.63) and stroke onset (1.11; 1.00-1.24), ischemic stroke death (2.15; 1.57-2.95), not associated with risk of ischemic stroke onset (1.07, 0.95-1.2), with no significant evidence of publication bias.
High salt intake is associated with significantly increased risk of stroke event. Further research should be directed toward clarifying and quantifying these possible effects and generating testable hypotheses on plausible biologic mechanisms.
c) Dietary Sodium and Risk of Stroke in the Northern Manhattan Study. Stroke. 2012; 43: 1200-1205
http://stroke.ahajournals.org/content/43/5/1200.longAbstract
Background and Purpose—The American Heart Association recommends limiting sodium intake to ≤1500 mg/day for ideal cardiovascular health. Although sodium intake has been linked to vascular disease by direct relationship with hypertension, few studies have supported an association with stroke risk.
Methods—Participants were from the Northern Manhattan Study (mean age 69± 10 years, 64% women, 21% white, 53% Hispanic, 24% black), a population-based cohort study of stroke incidence. Sodium intake was assessed with a food frequency questionnaire at baseline and evaluated continuously and categorically: ≤1500 mg/day (12%), 1501 to 2300 mg/day (24%), 2301 to 3999 mg/day (43%), and ≥4000 mg/day (21%). Over a mean follow-up of 10 years, we examined the association between sodium consumption and 235 strokes using Cox models adjusting for sociodemographics, diet, behavioral/lifestyle, and vascular risk factors.
Results—Of 2657 participants with dietary data, the mean sodium intake was 3031±1470 mg/day (median, 2787; interquartile range, 1966–3815 mg/day). Participants who consumed ≥4000 mg/day sodium had an increased risk of stroke (hazard ratio, 2.59; 95% CI, 1.27–5.28) versus those who consumed ≤1500 mg/day with a 17% increased risk of stroke for each 500-mg/day increase (95% CI, 1.07–1.27).
Conclusions—High sodium intake was prevalent and associated with an increased risk of stroke independent of vascular risk factors. The new American Heart Association dietary sodium goals will help reduce stroke risk.
6) Salt & ArteriosclerosisThe authors "suggest that excessive salt intake may be an important direct pathogenic factor for cardiovascular disease". These results suggest that an excessive salt intake promotes the overgrowth of fibrous tissue in the arteries, arterioles and other tissues and this fibrosis gradually over time makes the blood vessels increasingly stiff and eventually makes them more resistant to the flow of blood
a) Improved arterial distensibility in normotensive subjects on a low salt diet.
Arteriosclerosis. 1986 Mar-Apr;6(2):166-9.
http://www.ncbi.nlm.nih.gov/pubmed/3954670http://atvb.ahajournals.org/content/6/2/166.longAbstract
Arterial pulse wave velocity (PWV), a noninvasive index of arterial distensibility, was measured in 57 normotensive subjects who followed a voluntary low salt diet for a period ranging from 8 months to 5 years (mean, 24.8 months). Subjects who followed a regular diet were matched for age and mean arterial pressure with the low salt (LS) sample and were used as controls (C). For both samples, subjects were divided into three age groups: Group 1 (aged 2 to 19 years, n = 16), Group 2 (29 to 44 years, n = 26), and Group 3 (45 to 66 years, n = 15). There was a marked increase in aortic PWV with age in the control sample but not in the LS sample. There was no significant difference in aortic PWV for Group 1, but in Groups 2 and 3, the LS subjects showed a decrease of 21.8% and 22.7%, respectively, compared to C subjects. Aortic PWV (cm/sec) was: Group 1: C = 581 (SE44), LS = 614 (SE31); Group 2: C = 942 (SE46); LS = 737 (SE27) (p less than 0.001); Group 3: C = 958 (SE77), LS = 741 (SE25) (p less than 0.05]. Arm and leg PWV were also significantly lower in the older age groups. These findings suggest that normotensive adult subjects who follow a low salt diet (mean intake, 44 mmol Na/24 hours) have reduced arterial stiffness and that the effect is independent of blood pressure. This is prima facie evidence that reduced salt intake has a beneficial effect in improving distensibility of the central aorta and large peripheral arteries, which is independent of its antihypertensive action.
PMID: 3954670
b) Salt induces myocardial and renal fibrosis in the normotensive and hypertensive rats.
Circulation. 1998 Dec 8;98(23):2621-8.
Abstract
BACKGROUND:
The detrimental effects of high dietary salt intake may not only involve effects on blood pressure and organ hypertrophy but also lead to tissue fibrosis independently of these factors.
METHODS AND RESULTS:
The effect of a normal (1%) or high (8%) sodium chloride diet on myocardial and renal fibrosis was assessed by quantitative histomorphometry in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The effect of salt on transforming growth factor-beta1 (TGF-beta1) gene expression was assessed by Northern blot hybridization. A high-salt diet from 8 to 16 weeks of age resulted in increased blood pressure and left ventricular and renal hypertrophy in both WKYs and SHRs. Marked interstitial fibrosis was demonstrated in the left ventricle (LV), glomeruli, and renal tubules and in intramyocardial arteries and arterioles but not in the right ventricle. The collagen volume fraction increased significantly after high-salt diet in the LV, intramyocardial arteries and arterioles, glomeruli, and peritubular areas in both WKYs and SHRs. In the kidneys, glomerular and peritubular type IV collagen was also increased. There was overexpression of TGF-beta1 mRNA in the LV and kidneys in both rat strains after a high-salt diet (all P<0.001).
CONCLUSIONS:
High dietary salt led to widespread fibrosis and increased TGF-beta1 in the heart and kidney in normotensive and hypertensive rats. These results suggest a specific effect of dietary salt on fibrosis, possibly via TGF-beta1-dependent pathways, and further suggest that excessive salt intake may be an important direct pathogenic factor for cardiovascular disease.
PMID: 9843472
c) Effects of a low-salt diet on flow-mediated dilation in humans.
Am J Clin Nutr 2009;89:485-90
http://www.ncbi.nlm.nih.gov/pubmed/19106240Abstract
BACKGROUND:
The effect of salt reduction on vascular function, assessed by brachial artery flow-mediated dilatation (FMD), is unknown.
OBJECTIVE:
Our aim was to compare the effects of a low-salt (LS; 50 mmol Na/d) diet with those of a usual-salt (US; 150 mmol Na/d) diet on FMD.
DESIGN:
This was a randomized crossover design in which 29 overweight and obese normotensive men and women followed an LS diet and a US diet for 2 wk. Both diets had similar potassium and saturated fat contents and were designed to ensure weight stability. After each intervention, FMD, pulse wave velocity, augmentation index, and blood pressure were measured.
RESULTS:
FMD was significantly greater (P = 0.001) with the LS diet (4.89 +/- 2.42%) than with the US diet (3.37 +/- 2.10%), systolic blood pressure was significantly (P = 0.02) lower with the LS diet (112 +/- 11 mm Hg) than with the US diet (117 +/- 13 mm Hg), and 24-h sodium excretion was significantly lower (P = 0.0001) with the LS diet (64.1 +/- 41.3 mmol) than with the US diet (156.3 +/- 56.7 mmol). There was no correlation between change in FMD and change in 24-h sodium excretion or change in blood pressure. No significant changes in augmentation index or pulse wave velocity were observed.
CONCLUSIONS:
Salt reduction improves endothelium-dependant vasodilation in normotensive subjects independently of the changes in measured resting clinic blood pressure. These findings suggest additional cardioprotective effects of salt reduction beyond blood pressure reduction.
PMID: 19106240
d) Endothelial function is impaired after a high-salt meal in healthy subjects.
Am J Clin Nutr 2011;93:500-5.
http://www.ncbi.nlm.nih.gov/pubmed/21228265Abstract
BACKGROUND:
Dietary salt is related to blood pressure (BP), and cardiovascular disease and increased sodium intakes have been shown to impair vascular function. The effect of salt on endothelial function postprandially is unknown.
OBJECTIVE:
The aim was to investigate the postprandial effect of dietary salt on endothelial function as measured by flow-mediated dilatation (FMD) and peripheral arterial tonometry in healthy subjects.
DESIGN:
Sixteen healthy, normotensive subjects received a meal with added salt (HSM; 65 mmol Na) and a control low-salt meal (LSM; 5 mmol Na) on 2 separate occasions in a randomized order. Endothelial function was measured while fasting and postprandially at 30, 60, 90, and 120 min by using FMD and reactive hyperemia peripheral arterial tonometry. BP was also measured.
RESULTS:
Baseline FMD, reactive hyperemia index (RHI), and BP values were similar across interventions. Overall FMD was reduced 2 h postprandially. FMD was significantly more impaired after the HSM than after the LSM at 30 min [HSM (mean ± SD): 3.39 ± 2.44%; LSM: 6.05 ± 3.21%; P < 0.01] and at 60 min (HSM: 2.20 ± 2.77%; LSM: 4.64 ± 2.48%; P < 0.01). No significant differences in BP or RHI were observed between meals.
CONCLUSIONS:
An HSM, which reflects the typical amount of salt consumed in a commonly eaten meal, can significantly suppress brachial artery FMD within 30 min. These results suggest that high salt intakes have acute adverse effects on vascular dilatation in the postprandial state. This trial was registered at
http://www.anzctr.org.au/trial_view.aspx?ID=335115 as ACTRN12610000124033.
PMID: 21228265
E) Postprandial effects of a high salt meal on serum sodium, arterial stiffness, markers of nitric oxide production and markers of endothelial function. Dickinson KM1, Clifton PM2, Burrell LM3, Barrett PH4, Keogh JB5. Atherosclerosis. 2014 Jan;232(1):211-6. doi: 10.1016/j.atherosclerosis.2013.10.032. Epub 2013 Nov 20.
Abstract
AIM: The aim of the study was to determine if a high salt meal containing 65 mmol Na causes a rise in sodium concentrations and a reduction in plasma nitrate/nitrite concentrations (an index of nitric oxide production). Secondary aims were to determine the effects of a high salt meal on augmentation index (AIx) a measure of arterial stiffness and markers of endothelial function.
METHODS AND RESULTS: In a randomised cross-over study 16 healthy normotensive adults consumed a low sodium soup containing 5 mmol Na and a high sodium soup containing 65 mmol Na. Sodium, plasma nitrate/nitrite, endothelin-1 (ET-1), C-reactive protein (CRP), vasopressin (AVP) and atrial natriuretic peptide (ANP) concentrations before and every 30 min after the soup for 2 h. Blood pressure (BP) and AI were also measured at these time points. There were significant increases in serum sodium, osmolality and chloride in response to the high sodium meal. However plasma nitrate/nitrite concentrations were not different between meals (meal p = 0.812; time p = 0.45; meal × time interaction p = 0.50). Plasma ANP, AVP and ET-1 were not different between meals. AI was significantly increased following the high sodium meal (p = 0.02) but there was no effect on BP.
CONCLUSIONS: A meal containing 65 mmol Na increases serum sodium and arterial stiffness but does not alter postprandial nitrate/nitrite concentration in healthy normotensive individuals. Further research is needed to explore the mechanism by which salt affects vascular function in the postprandial period. This trial was registered with the Australian and New Zealand Clinical Trials Registry Unique Identifier:
ACTRN12611000583943http://www.anzctr.or ... ?ID=343019.
7) Salt, sodium, calcium & osteoporosis
https://www.drmcdougallforums.com/viewt ... =22&t=6508
8 ) Salt and Calcium Oxalate StonesEffects of a low-salt diet on idiopathic hypercalciuria in calcium-oxalate stone formers: a 3-mo randomized controlled trial.
Nouvenne A, Meschi T, Prati B, Guerra A, Allegri F, Vezzoli G, Soldati L, Gambaro G, Maggiore U, Borghi L.
Am J Clin Nutr. 2010 Mar;91(3):565-70. doi: 10.3945/ajcn.2009.28614. Epub 2009 Dec 30.
PMID:20042524
http://ajcn.nutrition.org/content/91/3/565.longhttp://ajcn.nutrition.org/content/early ... l.pdf+htmlhttp://ajcn.nutrition.org/content/suppl ... pp_1-2.docAbstract
BACKGROUND: A direct relation exists between sodium and calcium excretion, but randomized studies evaluating the sustained effect of a low-salt diet on idiopathic hypercalciuria, one of the main risk factors for calcium-oxalate stone formation, are still lacking.
OBJECTIVE: Our goal was to evaluate the effect of a low-salt diet on urinary calcium excretion in patients affected by idiopathic calcium nephrolithiasis.
DESIGN: Patients affected by idiopathic calcium stone disease and hypercalciuria (>300 mg Ca/d in men and >250 mg Ca/d in women) were randomly assigned to receive either water therapy alone (control diet) or water therapy and a low-salt diet (low-sodium diet) for 3 mo. Twenty-four-hour urine samples were obtained twice from all patients: one sample at baseline on a free diet and one sample after 3 mo of treatment.
RESULTS: A total of 210 patients were randomly assigned to receive a control diet (n = 102) or a low-sodium diet (n = 108); 13 patients (2 on the control diet, 11 on the low-sodium diet) withdrew from the trial. At the follow-up visit, patients on the low-sodium diet had lower urinary sodium (mean +/- SD: 68 +/- 43 mmol/d at 3 mo compared with 228 +/- 57 mmol/d at baseline; P < 0.001). Concomitant with this change, they showed lower urinary calcium (271 +/- 86 mg/d at 3 mo compared with 361 +/- 129 mg/d on the control diet, P < 0.001) and lower oxalate excretion (28 +/- 8 mg/d at 3 mo compared with 32 +/- 10 mg/d on the control diet, P = 0.001). Urinary calcium was within the normal range in 61.9% of the patients on the low-salt diet and in 34.0% of those on the control diet (difference: +27.9%; 95% CI: +14.4%, +41.3%; P < 0.001).
CONCLUSION: A low-salt diet can reduce calcium excretion in hypercalciuric stone formers.