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1.
Insights into Salt Handling and Blood Pressure.
Ellison, DH, Welling, P
The New England journal of medicine. 2021;(21):1981-1993
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Salt Transiently Inhibits Mitochondrial Energetics in Mononuclear Phagocytes.
Geisberger, S, Bartolomaeus, H, Neubert, P, Willebrand, R, Zasada, C, Bartolomaeus, T, McParland, V, Swinnen, D, Geuzens, A, Maifeld, A, et al
Circulation. 2021;(2):144-158
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Abstract
BACKGROUND Dietary high salt (HS) is a leading risk factor for mortality and morbidity. Serum sodium transiently increases postprandially but can also accumulate at sites of inflammation affecting differentiation and function of innate and adaptive immune cells. Here, we focus on how changes in extracellular sodium, mimicking alterations in the circulation and tissues, affect the early metabolic, transcriptional, and functional adaption of human and murine mononuclear phagocytes. METHODS Using Seahorse technology, pulsed stable isotope-resolved metabolomics, and enzyme activity assays, we characterize the central carbon metabolism and mitochondrial function of human and murine mononuclear phagocytes under HS in vitro. HS as well as pharmacological uncoupling of the electron transport chain under normal salt is used to analyze mitochondrial function on immune cell activation and function (as determined by Escherichiacoli killing and CD4+ T cell migration capacity). In 2 independent clinical studies, we analyze the effect of a HS diet during 2 weeks (URL: http://www.clinicaltrials.gov. Unique identifier: NCT02509962) and short-term salt challenge by a single meal (URL: http://www.clinicaltrials.gov. Unique identifier: NCT04175249) on mitochondrial function of human monocytes in vivo. RESULTS Extracellular sodium was taken up into the intracellular compartment, followed by the inhibition of mitochondrial respiration in murine and human macrophages. Mechanistically, HS reduces mitochondrial membrane potential, electron transport chain complex II activity, oxygen consumption, and ATP production independently of the polarization status of macrophages. Subsequently, cell activation is altered with improved bactericidal function in HS-treated M1-like macrophages and diminished CD4+ T cell migration in HS-treated M2-like macrophages. Pharmacological uncoupling of the electron transport chain under normal salt phenocopies HS-induced transcriptional changes and bactericidal function of human and murine mononuclear phagocytes. Clinically, also in vivo, rise in plasma sodium concentration within the physiological range reversibly reduces mitochondrial function in human monocytes. In both a 14-day and single meal HS challenge, healthy volunteers displayed a plasma sodium increase of [Formula: see text] and [Formula: see text] respectively, that correlated with decreased monocytic mitochondrial oxygen consumption. CONCLUSIONS Our data identify the disturbance of mitochondrial respiration as the initial step by which HS mechanistically influences immune cell function. Although these functional changes might help to resolve bacterial infections, a shift toward proinflammation could accelerate inflammatory cardiovascular disease.
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Randomised trial on effect of involving media reporters in salt reduction programme to increase media reports and the public's knowledge, belief and behaviors on salt and health: Changzhi reporters trial.
Li, Z, Feng, X, Wu, T, Yan, L, Elliott, P, Wu, Y
PloS one. 2021;(7):e0252989
Abstract
OBJECTIVE To assess the effects of a novel mass media intervention in increasing media reports on salt and health by involving media reporters in a scientifically well designed salt reduction trial. METHODS We recruited and trained 66 media reporters in Changzhi, Shanxi province, China to conduct a randomized controlled trial on blood pressure lowering effect of salt substitute in Dec, 2012 and Jan 2013 among their own relatives or friends (253 from 129 families in the salt substitute arm and 263 from 133 families in the control arm for two months). We shared trial results and other information on salt and health with the reporters within a month after the trial. We monitored all local newspapers for the number of relevant articles in 3 months before, 3 months during and 3 months after the intervention and at the 6th, 12th, 18th, 24th and 48th months after the intervention. Additionally, we conducted two independent surveys on knowledge, belief and behaviours of salt and health among local citizens before and after the intervention. RESULTS As expected, systolic blood pressure was reduced significantly more in the salt substitute than the control group (-4.7±11.0 mmHg vs -2.6±10.3 mmHg, p<0.001) in the randomized trial. The monthly mean number of relevant articles increased from 0.7 before to 1.7 during (p = 0.263), and further to 6.0 after the intervention (p<0.001), and varied from 2 (p = 0.170) to 4 (p = 0.008) from the 6th to 48th month; the awareness of knowledge on salt and health among local citizens improved significantly after the intervention. CONCLUSIONS Media reporters' participation in a well-designed salt reduction trial significantly increased the number of relevant media reports, and the effect was sustained for a prolonged period. Future mass media public health education programs should consider this innovative strategy for better and sustained impacts.
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Dietary salt intake increases with age in Japanese adults.
Sugiura, T, Takase, H, Ohte, N, Dohi, Y
Nutrition research (New York, N.Y.). 2021;:1-9
Abstract
Excess salt intake is linked to cardiovascular disease as well as hypertension, but whether individual salt intake increases with age has not been studied. The present study was designed to test the hypothesis that individual salt intake increases with age in Japanese adults. In this retrospective observational follow-up study, men and women age ≥30 years who participated in a baseline health checkup (2008-2009) at our center and had a health checkup 10 years later (n = 2598) were enrolled and salt intake was estimated by spot urine analysis. Yearly changes in salt intake were also assessed in participants with complete annual data over the course of 10 years from baseline (n = 1543). The follow-up study demonstrated increased salt intake (8.8 ± 2.0 to 9.3 ± 2.1 g/d, P < .001) with increasing age (54.0 ± 9.7 to 64.0 ± 9.8 years). Salt intake increased year over year in participants who had a health checkup annually for the 10-year follow-up period (n = 1543; analysis of variance, P < .001). Cross-sectional analyses using propensity-matched model revealed similar regional levels of salt intake in the baseline period (8.9 ± 2.0 g/d, 55.8 ± 11.4 years, n = 5018) and at 10 years (8.8 ± 2.0 g/d, P = .21; 55.9 ± 13.0 years, P = .65, n = 5105). These results suggest that dietary salt intake increases with age in Japanese adults, which should be considered in devising population-based strategies to lower dietary salt intake.
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Impact of an Innovative Equipment to Monitor and Control Salt Usage during Cooking at Home on Salt Intake and Blood Pressure-Randomized Controlled Trial iMC SALT.
Silva-Santos, T, Moreira, P, Pinho, O, Padrão, P, Abreu, S, Esteves, S, Oliveira, L, Norton, P, Rodrigues, M, Ndrio, A, et al
Nutrients. 2021;(1)
Abstract
(1) Background: Excessive salt consumption is associated with an increased risk of hypertension and cardiovascular disease, and it is essential to reduce it to the level recommended by the World Health Organization (<5 g/day). The main objective of this study is to verify the impact of an intervention, which used the Salt Control H equipment to reducing salt consumption; (2) Methods: The study was an 8-week randomized control trial with 114 workers from a public university. The intervention group (n = 57) used the equipment to monitor and control the use of salt during cooking (Salt Control H) at home for 8 weeks. The primary outcome was 24 h urinary sodium excretion as a proxy of salt intake. Secondary outcomes included changes in 24 h urinary potassium excretion, sodium to potassium ratio (Na:K), and blood pressure. (3) Results: There was a decrease in sodium intake after the intervention but with no statistical significance. When analyzing the results by sex and hypertension status, there was a reduction in sodium (-1009 (-1876 to -142), p = 0.025) and in Na:K ratio (-0.9 (-1.5 to -0.3), p = 0.007) in hypertensive men in the intervention group. (4) Conclusions: Interventions with dosage equipment can be valid approaches in individual salt reduction strategies, especially in hypertensive men.
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Sodium Reduction: How Big Might the Risks and Benefits Be?
Yin, X, Tian, M, Neal, B
Heart, lung & circulation. 2021;(2):180-185
Abstract
Cardiovascular diseases are the leading cause of death worldwide and raised blood pressure is the leading risk for these conditions. Excess sodium intake clearly elevates blood pressure though the association of sodium intake with cardiovascular outcomes has been disputed. Nonetheless, it was estimated that in 2017 excess dietary sodium caused between 1.4 and 5.4 million deaths. Key underlying assumptions for those estimates were that the association between sodium intake and cardiovascular disease is direct and linear, and that a daily consumption level of 2.0 g of sodium minimised risk. Recent data indicating that reported U-shaped associations of sodium with risk are the result of confounding provide strong support for the first assumption. Cardiovascular risks may, however, continue to decline below intake levels of 2.0 g per day. Further, because excess sodium intake appears to drive a progressive rise in blood pressure with age, the magnitude of the disease burden avoidable by sodium reduction may have been under-estimated. Regardless, health benefits will only be achieved if safe, effective and scalable interventions can be defined and none have been identified to date. Salt substitution, which switches regular salt for a reduced-sodium, added-potassium alternative offers a significant opportunity. Falls in blood pressure with salt substitution are comparable to single-drug therapy and salt substitutes are low cost, simple to use, well-tolerated and could be applied community-wide. Data that prove clinical benefits and exclude risks will be required to support widespread use. An ongoing large-scale randomised trial of the effects of salt substitution on stroke, major cardiovascular events and death will complete soon and define the role of salt substitutes in public health.
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Strategies for Reducing Salt and Sugar Intakes in Individuals at Increased Cardiometabolic Risk.
Ponzo, V, Pellegrini, M, Costelli, P, Vázquez-Araújo, L, Gayoso, L, D'Eusebio, C, Ghigo, E, Bo, S
Nutrients. 2021;(1)
Abstract
Non-communicable diseases (NCDs) are the first causes of death worldwide. Reduction in the dietary intake of salt and sugars is important lifestyle advice that is useful for NCD prevention. However, the simple recommendations of reducing salt and sugars by healthcare professionals are often ineffective; innovative strategies are therefore necessary. This review aimed at describing the current knowledge about the strategies to reduce dietary salt and sugar intake, including both strategies for the food industry to reduce the salt or sugar of its products and recommendations for health professionals in a clinical context, such as the replacement with substitutes in foods, the gradual reduction to allow a progressive consumer adaptation towards less intense taste, and the different spatial distribution of tastants within the food matrix with taste intensity enhancement. In addition, the cross-modal interaction between two or more different sensory modalities as an innovative strategy for enhancing sweetness and saltiness perception was described. Finally, the dietary tips for salt and sugar reduction were summarized in order to create a comprehensive guide of dietary advices for healthcare professionals for optimizing the management of patients at increased cardiometabolic risk.
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Homeopathy for Covid-19 in Primary Care: A structured summary of a study protocol for a randomized controlled trial.
Adler, UC, Adler, MS, Hotta, LM, Padula, AEM, de Toledo Cesar, A, Diniz, JNM, Mestre, CAA, Spiller, KR, Soares, L, de Freitas Santos, H, et al
Trials. 2021;(1):109
Abstract
OBJECTIVES To investigate the effectiveness and safety of homeopathic medicine Natrum muriaticum (LM2) for mild cases of COVID-19 in Primary Health Care. TRIAL DESIGN A randomized, two-armed (1:1), parallel, placebo-controlled, double-blind, clinical trial is being performed to test the following hypotheses: H0: homeopathic medicines = placebo (null hypothesis) vs. H1: homeopathic medicines ≠ placebo (alternative hypothesis) for mild cases of COVID-19 in Primary Care. PARTICIPANTS Setting: Primary Care of São Carlos - São Paulo - Brazil. One hundred participants aged 18 years or older, with Influenza-like symptoms and a positive RT-PCR for SARS-CoV-2. Willingness to give informed consent and to comply with the study procedures is also required. Exclusion criterium: severe acute respiratory syndrome. INTERVENTION AND COMPARATOR Homeopathy: 1 globule of Natrum muriaticum LM2 diluted in 20 mL of alcohol 30% and dispensed in a 30 ml bottle. Placebo: 20 mL of alcohol 30% dispensed in a 30 ml bottle. Posology: one drop taken orally every 4 hours (6 doses/day) while there is fever, cough, tiredness, or pain (headache, sore throat, muscle aches, chest pain, etc.) followed by one drop every 6 hours (4 doses/day) until the fourteenth day of use. The bottle of study medication should be submitted to 10 vigorous shakes (succussions) before each dose. Posology may be changed by telemedicine, with no break in blinding. Study medication should be maintained during home isolation. According to the Primary Care protocol, the home isolation period lasts until the 10th day after the appearance of the first symptom, or up to 72 hours without symptoms. MAIN OUTCOMES The primary endpoint will be time to recovery, defined as the number of days elapsed before all COVID-19 Influenza-like symptoms are recorded as mild or absent during home isolation period. Secondary measures are recovery time for each COVID-19 symptom; score of the scale created for the study (COVID-Simile Scale); medicines used during follow-up; number of days of follow-up; number of visits to emergency services; number of hospitalizations; other symptoms and Adverse Events during home isolation period. RANDOMISATION The study Statistician generated a block randomization list, using a 1:1 ratio of the two groups (denoted as A and B) and a web-based tool ( http://www.random.org/lists ). BLINDING (MASKING): The clinical investigators, the statistician, the Primary Care teams, the study collaborators, and the participants will remain blinded from the identity of the two treatment groups until the end of the study. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): One hundred participants are planned to be randomized (1:1) to placebo (50) or homeopathy (50). TRIAL STATUS Protocol version/date May 21, 2020. Recruitment is ongoing. First participant was recruited/included on June 29,2020. Due to recruitment adaptations to Primary Care changes, the authors anticipate the trial will finish recruiting on April 10, 2021. TRIAL REGISTRATION COVID-Simile Study was registered at the University Hospital Medical Information Network (UMIN - https://www.umin.ac.jp/ctr/index.htm ) on June 1st, 2020, and the trial start date was June 15, 2020. Unique ID: UMIN000040602. FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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High-salt intake affects retinal vascular tortuosity in healthy males: an exploratory randomized cross-over trial.
Wenstedt, EFE, Beugelink, L, Schrooten, EM, Rademaker, E, Rorije, NMG, Wouda, RD, Schlingemann, RO, Wong, TY, Vogt, L
Scientific reports. 2021;(1):801
Abstract
The retinal microcirculation is increasingly receiving credit as a relatively easily accessible microcirculatory bed that correlates closely with clinical cardiovascular outcomes. The effect of high salt (NaCl) intake on the retinal microcirculation is currently unknown. Therefore, we performed an exploratory randomized cross-over dietary intervention study in 18 healthy males. All subjects adhered to a two-week high-salt diet and low-salt diet, in randomized order, after which fundus photographs were taken and assessed using a semi-automated computer-assisted program (SIVA, version 4.0). Outcome parameters involved retinal venular and arteriolar tortuosity, vessel diameter, branching angle and fractal dimension. At baseline, participants had a mean (SD) age of 29.8 (4.4) years and blood pressure of 117 (9)/73 (5) mmHg. Overall, high-salt diet significantly increased venular tortuosity (12.2%, p = 0.001). Other retinal parameters were not significantly different between diets. Changes in arteriolar tortuosity correlated with changes in ambulatory systolic blood pressure (r = - 0.513; p = 0.04). In conclusion, high-salt diet increases retinal venular tortuosity, and salt-induced increases in ambulatory systolic blood pressure associate with decreases in retinal arteriolar tortuosity. Besides potential eye-specific consequences, both phenomena have previously been associated with hypertension and other cardiovascular risk factors, underlining the deleterious microcirculatory effects of high salt intake.
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Salt intake causes B-type natriuretic peptide elevation independently of blood pressure elevation in the general population without hypertension and heart disease.
Ohashi, N, Takase, H, Aoki, T, Matsuyama, T, Ishigaki, S, Isobe, S, Fujikura, T, Kato, A, Yasuda, H
Medicine. 2021;(19):e25931
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Abstract
Excessive salt intake causes hypertension and cardiovascular diseases (CVDs). B-type natriuretic peptide (BNP) is synthesized and released from the ventricle, and is a surrogate marker reflecting various CVDs. Moreover, when a slight BNP elevation is shown, it leads to a poor prognosis in the general population. However, the relationship between salt intake and BNP levels in the general population remains unclear, especially in those without hypertension and heart diseases.In this study, we recruited 1404 participants without hypertension and electrocardiogram abnormalities, who received regular annual health check-ups in Japan. Plasma BNP levels were measured, and daily salt intake levels were evaluated using urinary samples. In addition, some clinical parameters were obtained, and the data were cross-sectionally analyzed.The median of plasma BNP levels was 10.50 pg/mL, and daily salt intake was 8.50 ± 1.85 g. When dividing participants into quartiles according to daily salt intake, those with the highest daily salt intake revealed the highest plasma BNP levels. Plasma BNP levels were significantly and positively associated with daily salt intake. Moreover, multiple linear regression analyses revealed that plasma BNP levels showed a significant positive association with daily salt intake levels after adjustments.Plasma BNP levels were significantly and positively associated with daily salt intake after adjustment in the general population. Plasma BNP levels may be a surrogate marker reflecting salt-induced heart diseases.