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Purpose of Review: The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the burden of CVD., Recent Findings: Yet, since as long ago as 1988, and more recently in eight articles published in the European Heart Journal in 2020 and 2021, some researchers have propagated a myth that reducing sodium does not consistently reduce CVD but rather that lower sodium might increase the risk of CVD. These claims are not well-founded and support some food and beverage industry's vested interests in the use of excessive amounts of salt to preserve food, enhance taste, and increase thirst. Nevertheless, some researchers, often with funding from the food industry, continue to publish such claims without addressing the numerous objections. This article analyzes the eight articles as a case study, summarizes misleading claims, their objections, and it offers possible reasons for such claims. Our study calls upon journal editors to ensure that unfounded claims about sodium intake be rigorously challenged by independent reviewers before publication; to avoid editorial writers who have been co-authors with the subject paper's authors; to require statements of conflict of interest; and to ensure that their pages are used only by those who seek to advance knowledge by engaging in the scientific method and its collegial pursuit. The public interest in the prevention and treatment of disease requires no less., (© 2021. The Author(s).)

Seawater is rich in minerals which may help confer good palatability to foods, favouring the use of smaller amounts of salt, a recognized measure of cardiovascular prevention. The aim of this study was to investigate the nutritional properties, sensory characteristics and metabolic effects of a typical Neapolitan pizza prepared with seawater (SWP) in place of common salt, in comparison with Standard traditional Pizza (StP). The nutritional characteristics and the chemical profile of the SWP and StP were assessed by chemical analyses and the use of Food Composition Tables. Twelve healthy volunteers were recruited for a Randomized Controlled Trial, with the consumption of one StP and one SWP using a balanced crossover design. The satiating power and palatability of the two pizzas were tested by the administration of Visual Analogue Scales. Serum glucose, insulin and sodium were measured every 30 min and 3 h urines were collected after each meal. SWP contained nearly 50% less NaCl and a larger amount of micronutrients compared with StP. No significant differences were detected between the two pizzas with regard to satiating power, pleasantness and glycemic and insulinemic response. However, a significant difference was found in the urine volume collected over the 3 h after the two meals (194 mL after StP vs. 292 mL after SWP, p = 0.018) and in the 3 h sodium balance (+1.6 g after StP vs. +0.5 g after SWP, p = 0.002). Conclusions: SWP appears to be a food with favourable nutritional characteristics, very good acceptability and healthy metabolic properties: these results warrant confirmation by a larger intervention trial.

Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study). The study included 294 untreated normotensive non-diabetic men with normal renal function examined twice (1994-95 and 2002-04). Renal tubular Na handling was estimated by exogenous lithium clearance. Fractional reabsorption of Na in proximal and distal tubules was calculated and included in the analysis. At baseline, there was no association between BP and either proximal or distal fractional reabsorption of Na. At the end of the 8-year follow-up, direct associations were observed between baseline proximal (but not distal) Na fractional reabsorption and the changes occurred in systolic and diastolic BP over time (+2.79 and +1.53 mmHg, respectively, per 1SD difference in proximal Na-FR; p<0.01). Also multivariable analysis showed a direct association between baseline proximal Na fractional reabsorption and risk of incident hypertension, independently of potential confounders (OR: 1.34, 95%CI:1.06-1.70). The results of this prospective investigation strongly suggest a causal relationship between an enhanced rate of Na reabsorption in the proximal tubule and the risk of incident hypertension in initially normotensive men., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: PS is President of the Italian Society of Human Nutrition, scientific coordinator of the Interdisciplinary Working Group for Reduction of Salt Intake in Italy (GIRCSI), a member of the committee for the preparation of the Italian Nutritional Guidelines and an unpaid member of WASH (World Action in Salt and Health). FPC is Head of the World Health Organization Collaborating Centre for Nutrition, Vice-President and Trustee of the British Hypertension Society and unpaid member of CASH, WASH and the UH Health Forum. The remaining authors do not disclose any conflict of interest.

Objectives: To assess the reliability and reproducibility of estimations of group mean 24-h urinary sodium (Na) excretion through timed spot urines compared to 24 h urinary Na output in two independent cross-sectional population samples including men and women and different ethnic groups., Methods and Results: Study 1 was carried out in Britain and included 915 untreated 40-59 yrs male and female participants (297 white, 326 of black African origin and 292 South Asian). Study 2 was carried out in Italy and included 148 white men (mean age 58.3 yrs). All participants provided both a 24-h urine collection and a timed urine sample as part of population surveys. Na, creatinine (Cr) and volume (V) were measured in all samples. Age, body mass index (BMI) and blood pressure (BP) were also measured. We compared the daily Na excretion through 24-h urine (gold standard) with its estimate from timed urine samples with two methods: Tanaka's predictions and Arithmetic extrapolations, and assessed them with correlation coefficients, Bland-Altman plot, prediction of quintile position and Receiver Operating Characteristic (ROC) Areas Under the Curve (AUC) for a cut-off of <100 mmol of Na/day. In Study 1 (discovery study) with the Tanaka method there were poor correlations between predicted and measured 24-h Na excretions in different ethnic groups and genders (r Spearman from 0.055 [R(2) = 0.003] in black women to 0.330 [R(2) = 0.11] in white women). The Bland-Altman plots indicated consistent bias with overestimate for low and underestimate for high intakes. ROC AUCs varied from 0.521 to 0.652 with good sensitivity (95-100%) but very poor specificity (0-9%). With the Arithmetic extrapolations correlations varied from 0.116 [R(2) = 0.01] to 0.367 [R(2) = 0.13]. Bias was detected with both Bland-Altman plots and through quintile analyses (underestimate at low levels and overestimate at high levels). Finally, ROC AUCs varied from 0.514 to 0.640 with moderate sensitivity (64-70%) but low specificity (20-53%). In Study 2 (validation study) results were consistent with the discovery phase in white men., Conclusion: Based on these results, 24-h urinary collection for the measurement of Na excretion remains the preferred tool for assessing salt intake when compared with reported methods based on timed spot urine samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Genetic variation in alpha-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of alpha-adducin in controlling Na/K pump activity, wild-type or mutated rat and human alpha-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, alpha-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

Objective: The mechanisms underlying high blood pressure in the framework of metabolic syndrome (MS) are not clarified: we thus analyzed the relationship of MS and its components to renal tubular sodium handling among participants of the Olivetti Heart Study, an epidemiological investigation of a representative sample of adult white male population in southern Italy., Methods: Proximal (FPRNa) and distal (FDRNa) fractional sodium reabsorption were estimated by the clearance of exogenous lithium in 702 participants aged 25-75 years examined in 1994-1995. Blood pressure and relevant anthropometric and biochemical variables were also measured. The diagnosis of MS was based on modified National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) criteria., Results: FPRNa, but not FDRNa, was directly associated with body mass index (BMI), waist circumference, diastolic pressure, serum triglyceride and uric acid, independently of age and of antihypertensive treatment. After adjustment for age, FPRNa, but not FDRNa, was significantly greater in individuals with MS, as compared to those without [77.6% (95% confidence interval = 76.7-80.1) versus 74.4% (73.7-75.1), P < 0.001]. A similar difference was observed after the exclusion of participants on current antihypertensive treatment (P = 0.018). In untreated individuals, a significant interaction was observed between obesity and insulin resistance as related to FPRNa (P = 0.002): the highest age-adjusted levels of FPRNa were detected in obese hypertensive and obese insulin-resistant participants., Conclusion: In this sample of an adult male population, MS was associated with an increased rate of FPRNa. This finding is relevant to the pathophysiology of MS and possibly to the prevention of its cardiovascular and renal consequences.

Genes of the renin-angiotensin-aldosterone system (RAAS) are natural candidates for sodium homeostasis and blood pressure regulation. To investigate the effect of a combination of polymorphisms of RAAS genes on renal sodium handling and blood pressure, 918 participants to the Olivetti Heart Study were genotyped for the following polymorphisms: I/D of angiotensin converting enzyme (ACE), M235T of angiotensinogen (AGT), A1166C of angiotensin II type-1 receptor (AT1R), and C-344T of aldosterone synthase (CYP11B2). The segmental renal sodium handling was evaluated by the fractional excretions of exogenous lithium (FE-Li), uric acid (FE-UA), and sodium (FE-Na). Twenty-eight carriers of triple homozygosity for M (AGT), A (AT1R), and C (CYP11B2) in the presence of the D allele of ACE (DD/ID) showed lower FE-Li (20.0%+/-5.9% versus 25.0%+/-7.5%; P=0.004; mean+/-sD), FE-UA (6.3%+/-2.0% versus 8.2%+/-2.7%; P=0.001), and FE-Na (0.96%+/-0.41% versus 1.22%+/-0.61%; P=0.004) as compared with all other allelic combinations (n=890), independently from age and body mass, suggesting an enhanced rate of proximal tubular sodium reabsorption. The carriers of the MM, AA, CC, DD/ID combination showed a substantially higher probability of being hypertensive (OR: 3.4 [(99% CI: 1.1 to 10.1]), independently of age and body mass. This relatively rare combination of allelic variants of candidate genes of the RAAS is associated with a significant alteration in proximal renal sodium handling and with higher risk of hypertension, suggesting that a combination of polymorphic variants at different candidate loci may affect phenotypic expression even in the absence of detectable effects of each variant at any single locus.

Aim/hypothesis: Increased proximal renal sodium re-absorption is associated with central adiposity and insulin resistance in white men. Our study examined whether this association also exists in other ethnic groups with different prevalences of insulin resistance and associated metabolic abnormalities., Methods: We studied the association between fractional renal excretion of endogenous lithium (FELi) and metabolic syndrome in a population study of 1190 randomly selected men and women who where 40 to 59 years of age (426 white, 397 of African and 367 of South Asian origin). Anthropometric values, blood pressure, biochemical values, questionnaire data and timed urine collections were obtained with standardised techniques. Endogenous lithium in serum and urine was measured by absorption spectrophotometry. Metabolic markers were the homeostasis model assessment (HOMA) index, waist circumference, serum triglycerides, serum HDL cholesterol and metabolic syndrome as defined by Adult Treatment Panel III criteria., Results: In white men and women a higher rate of proximal sodium re-absorption was inversely associated with higher waist circumference, serum triglycerides and HOMA index, and with lower serum HDL cholesterol (all p< or =0.001). No associations were found in people of African or South Asian origin. The former had lower FELi than the other groups. White people with the metabolic syndrome had a lower FELi than those without (15.9% vs 19.0%; p=0.003). No difference was found in people of African or South Asian origin., Conclusions/interpretation: Increased proximal sodium re-absorption is associated with the metabolic syndrome in white men and women. This relationship is not seen in people of African or South Asian origin, despite a greater degree of insulin resistance.

A pathogenic role of the kidney in hypertension has been strongly supported by experimental studies by Guyton and Dahl since the 1960s. In the early 1980s, de Wardener and MacGregor proposed that in hypertensive patients the ability of the kidneys to excrete a sodium load could be genetically impaired. Since then, "sodium-sensitive" hypertension has been the object of numerous studies, mostly on animal models because of the difficulty to investigate the renal handling of sodium in humans. More recently, considerable progress in this field has been made thanks to the in vivo study of segmental renal tubular function by the clearance of lithium and to the growing knowledge of the genetics of renal tubular sodium transport systems. The scope of this review is to briefly review the most relevant information gathered by the investigation of segmental renal tubular sodium handling in humans as related to blood pressure regulation and hypertension. In aggregate, the results of these studies strongly support the association between altered renal sodium handling and high blood pressure and suggest a causal role of genetic, nutritional, metabolic, and neurohormonal factors. All of these factors, alone or in combination, may be able to impair the normal renal tubular sodium handling and influence blood pressure homeostasis. The paradigm of the pathogenic role of the kidney in hypertension is thus relentlessly shifting toward the definition of inherited as well as acquired renal tubular defects and molecular alterations, providing a plausible explanation for the alteration in blood pressure levels.

Objectives: Central adiposity, insulin resistance and hypertension are clearly interrelated but the mechanisms underlying this association have not been thoroughly elucidated. As renal sodium handling plays a central role in salt-sensitive forms of hypertension, we investigated the relation of renal tubular sodium handling to abdominal adiposity, blood pressure and insulin sensitivity., Design: Population-based study., Participants: Five hundred and fifty-five untreated Olivetti male workers, aged 25-75 years., Setting: Olivetti factory medical centers in Pozzuoli and Marcianise (Naples, Italy), Main Outcome Measures: Anthropometric indices, serum insulin, homeostatic model assessment index of insulin sensitivity, blood pressure, fractional excretions of uric acid and exogenous lithium (as markers of renal tubular sodium handling)., Results: In univariate analysis, measures of central adiposity (i.e. sagittal abdominal diameter and umbilical circumference) were directly correlated with serum insulin (P < 0.001) and blood pressure levels (P < 0.001) and inversely associated with the fractional excretions of uric acid and lithium (P = 0.01-0.001). In multiple linear regression analysis, the same anthropometric indices but not the measures of peripheral adiposity (arm circumference and tricipital skinfold thickness), were significant predictors of the fractional excretion of uric acid and lithium, independently of age, blood pressure and serum insulin levels (P = 0.01-0.001)., Conclusions: Abdominal adiposity was associated with altered renal tubular sodium handling apart from insulin resistance and high blood pressure. The data indicate that men with prevalent abdominal adiposity have an enhanced rate of tubular sodium reabsorption, mainly at proximal sites. These findings provide a possible mechanistic link between central adiposity and salt-dependent hypertension.

A higher prevalence of hypertension has been associated with the G-->A/GT (Gly40Ser) polymorphism of the glucagon receptor gene (GCGR) in two population studies. As the mutated receptor is less responsive to glucagon, it has been speculated that the increased susceptibility to hypertension is due to deprivation of the recognized natriuretic effect of the hormone. To test this hypothesis we determined the frequency of the polymorphic variant and evaluated the segmental renal sodium handling by the clearances of uric acid and of exogenous lithium in the Olivetti Heart Study participants (n=971). The polymorphic variant was present only in heterozygous form in 37 individuals (3.8%). After controlling for age and body mass index, the carriers of the variant were twice more likely to be hypertensive and almost three times more likely to be on antihypertensive treatment at the time of examination. Compared to participants carrying the wild type, those carrying the Gly40Ser allele had higher serum uric acid and lower fractional excretion of uric acid and exogenous lithium, independently of age, body mass, and current pharmacological treatment. We conclude that the Gly40Ser polymorphism of the GCGR gene is associated with higher risk of hypertension and with enhanced proximal tubular sodium reabsorption, a factor possibly contributing to hypertension in this group.

An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is associated with high blood pressure (BP) in cross-sectional investigations; however, its value as a predictor of future hypertension, and thus of cardiovascular risk, has not been defined. The present study evaluated the association between Na-Li CT and risk of future hypertension in a sample of 106 untreated normotensive middle-aged men participating in the Olivetti Prospective Heart Study in southern Italy. BP, anthropometric and metabolic variables, and RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994 through 1995. Na-Li CT was stable over time (r=0.85) and was significantly associated to systolic BP in both visits. Of the 106 initially normotensive participants, 14 were found to be hypertensive at the 8-year follow-up examination. Eleven of these 14 hypertensives were in the highest tertile of systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all significant predictors of the risk of future hypertension. Individuals with baseline systolic BP in the highest tertile had a 60% risk of developing hypertension if their Na-Li CT was also high, whereas their risk was only 5% if Na-Li CT was in the two lowest tertiles (P=0.003). RBC Na-Li CT was a valuable predictor of subsequent hypertension in middle-aged men with a high-normal BP level for their age.

An elevated red blood cell Na/Li countertransport (Na/Li CT) is often associated with high blood pressure and metabolic abnormalities. Recent studies suggested that a reduction in serum TG levels is associated with a decrease in Na/Li CT activity. However, it is still unclear if this phenomenon could be originated from systemic metabolic alterations or from modifications of the membrane dynamic properties. Aim of the present study was to investigate whether dietary or pharmacological TG lowering therapy might have a different effect on Na/Li CT activity and related metabolic parameters. Twenty normotensive hyper-TG patients were recruited from the Lipid outpatient Clinic: they had a baseline Na/Li CT activity significantly higher compared with age- and BMI-matched normolipidemic controls (386+/-33 vs 274+/-39 umol/l RBC/h, p<0.05). The patients were randomly prescribed one of the following two-months treatment: Group 1)-triglyceride lowering diet; Group 2)-lipid lowering drug (Gemfibrozil 600 mg b.i.d.). Na/Li CT and metabolic and anthropometric variables were measured at baseline and after 1 and 2 months of treatment. At the end of intervention, there was in both groups a significant and comparable fall in plasma triglyceride (group 1: -2.61+/-0.73 mmol/l p<0.01; group 2: -4.29+/-1.20 mmol/l p<0.01). In the diet-treated group there were, in addition small but significant reductions in body weight (-3.7+/-0.8 kg p<0.01), fasting glucose (-0.36+/-0.14 mmol/l p<0.05) and insulin levels (-2.1+/-0.5 mU/l, p<0.01), while no such changes were observed in the fibrate treated patients. Na/Li CT activity was significantly and comparably reduced at the end of treatment in both groups (group 1: -97+/-28 umol/l cell/h, p<0.01; group 2: -89+/-30 umol/l cell/h, p<0.01). In conclusion, these results indicate that the decrease in Na/Li CT associated with both dietary and drug treatment of hypertriglyceridemia is to be traced to a direct effect of plasma TG concentration on this transport system (probably as a result of modification in the membrane lipid environment) rather than to changes in plasma insulin levels or insulin resistance.

A significant and positive association between red blood cell sodium lithium countertransport (Na-Li CT) and blood pressure has been found in numerous studies. However, the majority of the studies presented to date are cross-sectional in nature and limited information exists on the longitudinal association between Na-Li CT and blood pressure. The present study analyzes the longitudinal association between Na-Li CT and blood pressure in 124 men participants in the Olivetti Heart Study and normotensives at the baseline examination. The Na-Li CT measured at the 12 year follow-up examination was analyzed in regard to the blood pressure changes over time during the 12 year follow-up. Na-Li CT (measured at follow-up examination) was positively related to changes over time in systolic pressure (r = 0.16) and diastolic pressure (r = 0.07) and changes in body mass index (r = 0.18). When blood pressure changes over time were analyzed by tertiles of Na-Li CT, the highest tertile group exhibited on the average significantly higher increases in systolic blood pressure compared with participants of the lowest tertile of the Na-Li CT distribution. This difference remained statistically significant after adjusting for the changes in weight observed during the 12 years follow-up. These findings indicate that the Na-Li CT distribution is related to blood pressure changes over time. However, the usefulness of Na-Li CT as a predictor of incidence of hypertension remains to be established.

Objective: To explore the relationship between fractional lithium excretion (taken as an index of proximal sodium excretion), blood pressure and metabolic risk factors for coronary heart disease in a sample of a general white male population., Design: A cross-sectional survey of a sample of a white male working population carried out as part of the Olivetti Heart Study., Setting: The Olivetti factory in Pozzuoli, a suburb of Naples, Italy., Participants: Five hundred and sixty-seven untreated white male workers aged 21-68 years., Measurements: Anthropometry, blood pressure, a blood test to determine the lipid profile, electrolytes, glucose and uric acid levels, a detailed questionnaire and urinary measurements on a fasting timed urine sample after a 300 mg lithium carbonate capsule taken the night before the investigation., Results: The fractional excretion of lithium was inversely associated with body weight, body mass index, diastolic blood pressure, serum triglycerides level and serum uric acid level whereas it was positively associated with serum high-density lipoprotein cholesterol level. The greater the percentage of filtered sodium reabsorbed at the proximal tubule the greater the overall metabolic cardiovascular risk. The association was consistent across tertiles of fractional excretion of lithium, was independent of age, smoking, alcohol consumption and sodium excretion (taken as an index of sodium intake) and persisted in multiple regression analysis. Men with high serum triglycerides, high serum uric acid and low serum high-density lipoprotein cholesterol levels and higher blood pressure had significantly lower fractional excretion of lithium (and thus enhanced proximal sodium reabsorption) than did men with a normal metabolic profile (21.8 +/- 5.6 versus 26.5 +/- 5.1%, p = 0.002)., Conclusions: The independent association between a cluster of risk factors for cardiovascular disease suggestive of insulin resistance and increased proximal sodium reabsorption at the renal tubule indicates a new feature of the metabolic syndrome that, if causal, could be amenable to intervention.

The objective of this study was to investigate the relationships between erythrocyte Na-Li countertransport, plasma renin activity (PRA), plasma aldosterone and plasma atrial natriuretic peptide (ANP) in a population-based study, in a cross-sectional observation of a randomly selected sample of a male working population, conducted at the Medical Care Center at the Olivetti Factory in Pozzuoli (Naples). One hundred and seventy-nine male employees aged 45.3 +/- 6.8 years (mean +/- SD), all on unrestricted diet and on no pharmacological treatment were studied. Statistical associations between Na-Li countertransport activity and the hormonal factors being studied were investigated, with control for the possible confounding effects of age, BP and sodium intake. Na-Li countertransport was significantly and positively associated with plasma aldosterone concentration (r = 0.228, P < 0.01) but not with PRA or plasma ANP. Men in the highest quartile of the Na-Li countertransport distribution had significantly higher plasma aldosterone levels than men in the other quartiles (P < 0.01) and this difference was independent of age, body mass, PRA, urinary sodium excretion and blood pressure. It is concluded that plasma aldosterone levels are enhanced and disproportionately high relative to plasma renin activity in individuals with high Na-Li countertransport, independently of known potential confounders.

Objective: To define the relationship, if any, between uric acid metabolism (serum and urinary levels) and proximal tubular sodium handling in a sample of general male population., Design: Cross-sectional survey of a sample of the male working population conducted as part of a nationwide survey of the prevalence of cardiovascular risk factors., Setting: The Olivetti factory in Pozzuoli, a suburb of Naples, Italy., Participants: Five hundred sixty-eight untreated male workers aged 21 to 68 years (90.8% of those eligible)., Measurements: Anthropometry, blood pressure, blood tests, a detailed questionnaire, and urinary measurements on a fasting timed collection after a 300-mg lithium carbonate capsule was taken the night before the investigation., Results: Serum uric acid level was inversely and significantly associated with the fractional excretion of lithium (r = -.22, P < .001), ie, the higher the serum uric acid level, the greater the amount of sodium reabsorbed at nephron sites proximal to the distal tubule. The association was graded and independent of possible confounders such as age, body mass, smoking, wine consumption, blood pressure, fractional excretion of sodium, and serum creatinine (R2 = .34, P < .001)., Conclusions: High serum uric acid levels are independently associated with increased proximal tubular sodium reabsorption in men. This relationship suggests an altered tubular sodium handling and uric acid metabolism consistent with hyperinsulinemia, insulin resistance being the possible pathophysiological link.

1. A human lymphocyte preparation, obtained by Percoll gradient centrifugation and free of contaminating monocytes and granulocytes, was used to study the kinetics of the Na(+)-H+ exchanger through activation by nigericin-induced acidic loading. The fluorescent probe biscarboxyethylcarboxyfluorescein (acetoxymethyl ester) was used to determine cell pH and buffering capacity and to measure Na(+)-H+ exchange activity as external Na(+)-dependent H+ efflux. 2. At a cell pH of 6.2, H+ efflux was stimulated by external Na+ with a Km of 30 mmol/l (SEM 6, n = 3) and a calculated Vmax. of 0.73 mmol s-1 l-1 of cell water (SEM 0.06, n = 6). External Na(+)-dependent H+ efflux was more than 98% inhibited and half-maximally inhibited by 200 mumol/l and 17 mumol/l amiloride, respectively. The external pH also inhibited Na(+)-H+ exchange, with a Ki of 93 nmol/l. 3. Na(+)-H+ exchange was sigmoidally activated by an internal pH lower than 7.0 with a Hill coefficient of 2.14 (SEM 0.15, n = 6) and a pK of 6.57 (SEM 0.03, n = 6). Cell buffering capacity was also measured as a function of cell pH and found to gradually increase from 14 to 26 mmol l-1 of cell water pH-1 when cell pH fell below 6.6. The maximal transport rate (cell pH 6.0-6.2) was 0.50 mmol (s l of cell water)-1 (SEM 0.08, n = 12) and ranged between 0.25 and 1.10.(ABSTRACT TRUNCATED AT 250 WORDS)

The renal fractional excretion of uric acid was determined for both a habitual diet and an NaCl-restricted diet in two groups of untreated subjects with low (117-207 mumol per litre of cells per h) and high (373-598 mumol per litre of cells per h) erythrocyte Na-Li countertransport identified in a population-based survey of middle-aged male workers. The group with high Na-Li countertransport had a higher mean blood pressure (P less than 0.05); this group also had a significantly reduced fractional excretion of uric acid with the NaCl-restricted diet even after adjustment for the difference in blood pressure (P less than 0.03). These findings are compatible with an abnormality in kidney tubular function and possibly in the renal handling of sodium in subjects with elevated erythrocyte Na-Li countertransport.

The relationship between segmental renal tubular sodium handling (using the renal clearance of ingested lithium as a marker of proximal tubular sodium handling) and circulating plasma levels of atrial natriuretic factor (ANF) was studied in a sample of 295 untreated men drawn from a male population at work under their usual living conditions. Plasma ANF was positively and significantly related to sodium excretion at the distal nephron, indicating that this hormone interacts with a distal renal tubular site to influence the control of sodium excretion in man.

This study focuses on the relationship between some aspects of intra-erythrocytic sodium metabolism (intra-erythrocytic Na content, Na,Li-countertransport), blood pressure, and family history of hypertension, in a group of 84 randomly selected school children (45 males, 39 females). Na,Li-countertransport was significantly related to both systolic blood pressure (SBP) and diastolic blood pressure (DBP) only in boys at the univariate level, but both of these associations lost statistical significance after the possible confounding role of weight and height were taken into consideration. In both sexes, participants with a family history of hypertension had similar values of both intra-erythrocytic Na content and Na,Li-countertransport to participants with no family history. We conclude that family history of hypertension does not seem to play an important role in the determination of either intra-erythrocytic Na content or Na,Li-countertransport at this age. Although the positive association between Na,Li-countertransport and blood pressure observed in adult males is already present in childhood, this probably is still, at least in part, dependent upon body size.

The relationship of red blood cell (RBC) Na/Li countertransport to the renal handling of lithium and uric acid was investigated in a sample of 176 untreated men. Subjects in the upper quintile of the Na/Li countertransport distribution (n = 40), compared to those in the two lower quintiles (n = 72), had higher serum uric acid levels (0.34 +/- 0.06 v 0.29 +/- 0.05 mmol/L, P less than 0.001) and systolic blood pressure (131 +/- 19 v 123 +/- 16 mm Hg, P less than 0.02) and slightly lower fractional excretion of uric acid (7.5 +/- 1.5 v 8.4 +/- 2.6%, P less than 0.08). The lithium fractional excretion was not significantly related to either blood pressure or RBC Na/Li countertransport. The altered uric acid metabolism in individuals with high RBC Na/Li countertransport could be the expression of an abnormality of renal tubular function.

The variability of 24-hour urinary sodium, potassium, and calcium excretion was studied in a sample of 22 Neapolitan men with mild blood pressure elevation. On 5 days within a 1-month period, 24-hour urine specimens were collected by each subject. The estimated ratio of intraindividual-to-interindividual variance was 1.12 for urinary sodium, 2.46 for urinary potassium, and 0.52 for urinary calcium. Based on these values, five 24-hour urine collections are necessary to reduce to less than 10% the diminution of the correlation coefficient between urinary sodium and another related variable; this number is substantially lower than that found in previous studies in a North American population sample, but similar to the one reported for Chinese population samples. Ten urinary collections are needed for potassium excretion. A different and more favorable situation is observed for 24-hour calcium excretion, as only two collections are necessary for the adequate characterization of individuals in a population.

1. It has been proposed that the enhanced erythrocyte Na+/Li+ countertransport observed in many patients with essential hypertension could be a marker of abnormal renal proximal tubular function. We thus investigated the relationship of blood pressure and Na+/Li+ countertransport to an index of proximal tubular function such as renal Li+ clearance. 2. The study was carried out in a sample of 299 untreated male subjects (aged 21-59 years) randomly selected from a population at work. Na+/Li+ countertransport was measured in a representative sub-group of 176 men. 3. We did not detect statistically significant correlation of either blood pressure or Na+/Li+ countertransport (Vmax) with fractional excretion of Li+, while confirming the existence of a significant continuous association of blood pressure and body mass index with Na+/Li+ countertransport (P less than 0.01). 4. A sub-sample of 57 participants belonging to the lowest or the highest quintiles of Na+/Li+ countertransport distribution repeated the Li+ clearance study after moderate Na+ restriction. 5. Although fractional excretions of Na+ and Li+ were reduced on the low Na+ diet (both P less than 0.001), they did not differ significantly between groups. 6. Our results are at variance with the findings of a recent case-control study in a young age group and suggest that further studies are necessary before a conclusion can be drawn as to the suitability of Na+/Li+ countertransport as a marker of Na+ reabsorption in the renal proximal tubule.

Abstract Background Blood pressure is a primary cardiovascular disease risk factor. Population-wide governmental strategies aim to reduce lifestyle and dietary risk factors for hypertension, one of which is an unbalanced diet with high sodium and low potassium intakes. Nutrition interventions in the workplace are considered a promising approach in encouraging health-promoting behaviors. We developed and conducted the health promoting sodium reduction trial “Healthful & Tasty: Sure!” in worksites in the German-speaking part of Switzerland from May 2015 to Nov 2016, for which we present the study protocol and baseline characteristics. Methods Healthful & Tasty, a cluster nonrandomized single-arm trial with calibration arm, aimed to demonstrate the effectiveness of a combined educational and environmental intervention in the workplace in reducing employees’ average daily sodium/salt intake by 15%. To this end, health and food literacy of employees and guideline compliance among the catering facility team needed to be improved. The primary outcome measure was sodium/salt intake estimated from sodium excretion in a 24-h urine sample. Secondary outcome measures included changes in the overall qualitative diet composition, blood pressure, anthropometric indices, and health and food literacy. Of eight organizations with catering facilities, seven organizations took part in the nutrition education and catering salt reduction interventions, and one organization participated as a control. Overall, 145 consenting employees were included in the staggered, one-year four-phase trial, of which 132 participated in the intervention group. In addition to catering surveys and food sampling, the trial included five follow-up health assessments including questionnaires, blood pressure measurements, anthropometrics, and sodium, potassium, and iodine intake measurements obtained from 24-h and spot urine samples, and a food record checklist. Exploratory and hypothesis generating baseline statistical analysis included 141 participants with adequate 24-h urine samples. Discussion Despite practice-driven limitations to the study design and small cluster and participant numbers, this trial has methodological strength and will provide important insights into the effectiveness of a combined educational and environmental intervention to reduce salt intake among female and male Swiss employees. Trial registration German Clinical Trials Register, DRKS00006790. Registered 23 September 2014.

Excess salt intake is the leading dietary risk factor for cardiovascular disease in most countries, including Italy. While the cost-effectiveness of interventions aimed to reduce salt intake has been proved, the WHO recommendation to reduce salt intake by 30 % at the global level by 2025 is far from being reached. In Italy, two surveys of the general adult population have established that the average salt intake is still almost twice the WHO recommendation although it was reduced by 1.2 g/day between 2008–12 and 2018–19. Previous investigations had shown that non-discretionary salt added by the industry or by local craft producers represents at least 50 % of the total intake and indicated cereal-based products as the main source of non-discretionary salt. Two recent studies conducted by the Italian Society of Human Nutrition "Young Working Group" have provided updated information on the salt content of almost three thousand cereal-based products currently available on the Italian food market and shown that most of the items evaluated had a sodium content much higher than the sodium benchmarks recently proposed by WHO. Italy has built the foundations of an effective population strategy for salt intake reduction: it is time however to proceed with full commitment to food reformulation if any substantial further progress has to be made. Salt benchmarks for Italy need to be defined for the food categories most relevant to population salt intake and their implementation should ideally be mandatory after consultation with food producers. • Average salt intake in Italy is still almost twice the WHO recommended level. • Cereal-based products are the major source of non-discretionary salt intake in Italy. • The sodium content of cereal-based products is in almost all cases well above the benchmarks proposed by WHO. • There is an urgent need to proceed to food reformulation by defining sodium targets for the foods most relevant to high salt intake. [ABSTRACT FROM AUTHOR]

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Aims: In the course of the COVID-19 pandemic, multiple suggestions have been delivered through websites and social media referring to natural substances and various kinds of supplements with thaumaturgical properties in preventing and/or fighting the coronavirus infection. Indeed, there is no clinical trial evidence that a dietary or pharmacological supplementation of any particular substance will increase the effectiveness of the immune defences. There are however three nutritional issues that deserve special attention under the present circumstances, namely vitamin D deficiency, excess salt intake and inappropriate alcohol consumption. Here is a short review of the current knowledge about the possible role of these factors in the immunity defence system and their potential impact on the modulation of the immune response to SARS-COV2 infection.Data Synthesis: For all of these factors there is convincing evidence of an impact on the immune defence structure and function. In the absence of RCT demonstration that increased ingestion of any given substance may confer protection against the new enemy, special attention to correction of these three nutritional criticisms is certainly warranted at the time of COVID pandemic.Conclusions: We propose that the inappropriate intake of salt and alcohol and the risk of inadequate vitamin D status should be object of screening, in particular in subjects at high mortality risk from SARS-COV 2 infection, such as institutionalised elderly subjects and all those affected by predisposing conditions. [ABSTRACT FROM AUTHOR]

Background and Aims: High sodium (Na) and low potassium (K) intake are associated with hypertension and CVD risk. This study explored the associations of health literacy (HL), food literacy (FL), and salt awareness with salt intake, K intake, and Na/K ratio in a workplace intervention trial in Switzerland.Methods and Results: The study acquired baseline data from 141 individuals, mean age 44.6 years. Na and K intake were estimated from a single 24-h urine collection. We applied validated instruments to assess HL and FL, and salt awareness. Multiple linear regression was used to investigate the association of explanatory variables with salt intake, K intake, and Na/K. Mean daily salt intake was 8.9 g, K 3.1 g, and Na/K 1.18. Salt intake was associated with sex (p < 0.001), and K intake with sex (p < 0.001), age (p = 0.02), and waist-to-height ratio (p = 0.03), as was Na/K. HL index and FL score were not significantly associated with salt or K intake but the awareness variable "salt content impacts food/menu choice" was associated with salt intake (p = 0.005).Conclusion: To achieve the established targets for population Na and K intake, health-related knowledge, abilities, and skills related to Na/salt and K intake need to be promoted through combined educational and structural interventions. Clinical Trials Registry number: DRKS00006790 (23/09/2014). [ABSTRACT FROM AUTHOR]

Summary: Background & aims: Systematic reviews of case–control studies evaluating the relationship between dietary salt intake and gastric cancer showed a positive association, however a quantitative analysis of longitudinal cohort studies is lacking. Therefore, we carried out a meta-analysis to assess the association between habitual salt intake and risk of gastric cancer in prospective studies. Methods: We performed a systematic search of published articles (1966–2010). Criteria for inclusion were: original articles, prospective adult population studies, assessment of salt intake as baseline exposure and of gastric cancer as outcome, follow-up of at least 4 years, indication of number of participants exposed and events across different salt intake categories. Results: Seven studies (10 cohorts) met the inclusion criteria (268 718 participants, 1474 events, follow-up 6–15 years). In the pooled analysis, “high” and “moderately high” vs “low” salt intake were both associated with increased risk of gastric cancer (RR = 1.68 [95% C.I. 1.17–2.41], p = 0.005 and respectively 1.41 [1.03–1.93], p = 0.032), with no evidence of publication bias. The association was stronger in the Japanese population and higher consumption of selected salt-rich foods was also associated with greater risk. Meta-regression analyses did not detect specific sources of heterogeneity. Conclusions: Dietary salt intake was directly associated with risk of gastric cancer in prospective population studies, with progressively increasing risk across consumption levels. [Copyright &y& Elsevier]

Abstract: Excess dietary sodium chloride (salt) intake is etiologically related to hypertension and cardiovascular disease (CVD). Moderate reduction of salt intake reduces blood pressure (BP) and is expected to contribute to reduce the risk of CVD. Previous community-based trials to reduce BP by means of salt reduction were very successful. The initial positive results of national strategies of dietary salt intake reduction in several European countries, driven by the initiative of the World Health Organisation (WHO) and non-governmental organisations such as the World Action of Salt and Health (WASH), have paved the way for action in other European Union (EU) member states. In Italy, several initiatives aiming at reduction of salt intake at the population level have been recently undertaken. These initiatives include i) the evaluation of current dietary habits promoted by the Working Group for Dietary Salt Reduction in Italy (GIRCSI); ii) the chemical analysis of the bread salt content, a major source of sodium intake in Italy, and the agreement between the bakers’ associations and the Ministry of Health for a gradual reduction of the bread salt content; iii) the implementation of educational campaigns to increase population awareness, iv) the involvement of the food catering system. In the immediate future, food reformulation must be extended to other food categories in collaboration with industry, foods’ salt targets ought to be defined, the food labelling system must be improved and population salt awareness must be further increased through educational campaigns. The GIRCSI Working Group is committed to pursue these objectives. [Copyright &y& Elsevier]