Some time ago, a well-known American newspaper titled "Salt killer" and explained in detail the reasons why the abuse of common kitchen salt could cause serious damage to health.In fact, the salt is found in nature in almost all the foods for which we take daily, but a strong consumption can damage the human body.

I will mention briefly some recent studies that agree with all the scientific literature of previous years.

Let's start with a recommendation sound : the World Health Organization recommends sodium intake reduction in the population as a key strategy to reduce the burden of cardiovascular diseases.

The World Health Organization outlines as main aspects of obesity:

• Worldwide obesity has nearly tripled since 1975.
  
• In 2016, more than 1.9 billion adults, 18 years and older, were overweight. Of these over 650 million were obese.
  
• 39% of adults aged 18 years and over were overweight in 2016, and 13% were obese.
  
• Most of the world's population live in countries where overweight and obesity kills more people than underweight.
  
• 41 million children under the age of 5 were overweight or obese in 2016.
  
• Over 340 million children and adolescents aged 5-19 were overweight or obese in 2016.
  
• Obesity is preventable reducing the fat, sugar and salt content of processed foods (1).

However, there is a debate around this recommendation, as the sensitivity of blood pressure to sodium intake has been shown to vary between individuals, suggesting that sodium intake reduction should be targeted at individuals with certain clinical conditions, instead of the whole population. For instance, it has been shown that older adults with elevated blood pressure, diabetes, or chronic kidney disease have a blood pressure that is more sensitive to a reduction in sodium intake than adults without these conditions (2). 

It is therefore appropriate to examine the scientific literature, category by category.

Salt in childrens and adolescents

Ten studies were conducted in children with elevated blood pressure without identifiable cause, two in children with familial hypertension, one in children with at least one cardiovascular risk factor, one in children with chronic renal insufficiency, one in children with urolithiasis, and one in premature infants. A positive association between sodium intake and blood pressure was found in all studies, except one. The meta‐analysis of six studies among children with elevated blood pressure without identifiable cause revealed a difference of 6.3 mm Hg (95% CI 2.9‐9.6) and 3.5 mm Hg (95% CI 1.2‐5.7) in systolic and diastolic blood pressure, respectively, for every additional gram of sodium intake per day. In conclusion, our results indicate that the blood pressure response to salt is greater in children with clinical conditions, mainly hypertension, than in those without associated clinical conditions (3).

Sodium is the most abundant extracellular cation and therefore pivotal in determining fluid balance. At the beginning of life, a positive sodium balance is needed to grow. Newborns and preterm infants tend to lose sodium via their kidneys and therefore need adequate sodium intake. Among older children and adults, however, excessive salt intake leads to volume expansion and arterial hypertension. Children who are overweight, born preterm, or small for gestational age and African American children are at increased risk of developing high blood pressure due to a high salt intake because they are more likely to be salt sensitive. In the developed world, salt intake is generally above the recommended intake also among children. Although a positive sodium balance is needed for growth during the first year of life, in older children, a sodium-poor diet seems to have the same cardiovascular protective effects as among adults. This is relevant, since: 

a blood pressure tracking phenomenon was recognized; 

the development of taste preferences is important during childhood; 

salt intake is often associated with the consumption of sugar-sweetened beverages (predisposing children to weight gain) (2).

Salt in adults

Most adults in the United States, including those with hypertension, consume sodium in excess of the recommended 2300 mg/d, with the mean daily sodium intake being ∼3500 mg. High sodium intake is known to be associated with high blood pressure. In 2013, the Institute of Medicine concluded that there was evidence to support an association between sodium intake and an increased risk of cardiovascular disease, stroke, and all-cause mortality in accordance with the known effects of sodium on blood pressure. This study provides evidence that suggests that sodium intake may affect the gut microbiome. 4-Ethylphenylsulfate increased with sodium restriction and was the most strongly associated with change in sodium intake.Metabolites in the γ-glutamyl amino acid metabolite group decreased with lower sodium intake. Metabolites within the tryptophan metabolism pathway, particularly indole-related metabolites, significantly increased with sodium restriction. In conclusion, metabolites and associated metabolic pathways differed by sodium intake (4).

Salt in the elderly

Salt intake has been implicated in the pathogenesis of abdominal aortic aneurysm (AAA) through studies in rodent models but not previously studied in humans. The aim of this study was to examine the association between reported addition of salt to food and the prevalence of AAA. A risk factor questionnaire which contained a question about salt intake was included as part of a population screening study for AAA in 11742 older men. AAA presence was assessed by abdominal ultrasound imaging using a reproducible protocol. Conclusion
Reported salt intake is associated with AAA in older men (5).

Salt in pregnancy

Previous laboratory studies demonstrated that dietary salt overload and salt restriction during pregnancy were associated with cardiac and renal structural and/or functional alterations in adult offspring. The present study evaluated renal and cardiac structure and the local renin-angiotensin system in newborns from dams fed high-, normal- or low-salt diets during pregnancy. Conclusion : high salt intake during pregnancy induced left and right ventricular hypertrophy in male newborns. Salt restriction during pregnancy reduced the expression of renal angiotensin II receptors in newborns (6).

It was hypothesized that primary renal sodium retention blunted the reactivity of the renin-angiotensin-aldosterone system to changes in salt intake in preeclampsia (PE). A randomized, cross-over, double-blinded, dietary intervention design was used to measure the effects of salt tablets or placebo during low-salt diet in PE patients (n = 7), healthy pregnant women (n = 15), and nonpregnant women (n = 13). High-salt intake decreased renin and angiotensin II concentrations significantly in healthy pregnant women (P < .03) and in nonpregnant women (P < .001), but not in PE (P = .58), while decreases in aldosterone and increases in brain natriuretic peptid (BNP) were similar in the groups. In PE patients, uterine and umbilical artery indices were not adversely changed during low-salt diet. Creatinine clearance was significantly lower in PE with no change by salt intake. PE patients displayed alterations of plasma renin and angiotensin II in response to changes in dietary salt intake compatible with a primary increase in renal sodium reabsorption in hypertensive pregnancies (7).

Is salt responsible for hypertension?

The studies are discordant.

For decades the notion that an excessive consumption of salt (NaCl) leads to hypertension has persisted. However, this idea is based on opinion, not scientific proof. Despite this, every health organization, agency, and clinicians around the world have been advising salt restriction, especially to hypertensive patients. The present review article suggests that the consumption of a high-salt diet is not the cause of hypertension and that there are other factors, such as added sugars, which are causative for inducing hypertension and cardiovascular disease (8).

It has been known that salt-sensitivity of blood pressure is defined genetically as well as can be developed secondary to either decreased renal function or by influence of other environmental factors. The aim of the study was to evaluate the possible mechanism for the development of salt-sensitive essential hypertension in the population of Georgia. The Case-Control study included 185 subjects, 94 cases with Essential Hypertension stage I (JNC7) without prior antihypertensive treatment, and 91 controls. Salt-sensitivity test was used to divide both case and control groups into salt-sensitive (n=112) and salt-resistant (n=73) subgroups. Endogenous cardiotonic steroids, sodium and PRA were measured in blood and urine samples at the different sodium conditions. Determinations of circulating levels of endogenous sodium pump inhibitors and PRA were carried out using the ELISA and RIA methods. Descriptive statistics were used to analyze the data. Differences in variables between sodium conditions were assessed using paired t-tests. Salt-sensitivity was found in 60.5% of total population investigated, with higher frequency in females. Salt-sensitivity positively correlated with age in females (r=0.262, p<0.01). Statistically significant positive correlation was found between 24 hour urine sodium concentration changes and salt-sensitivity r=0.334, p200 mmol) which is typical in traditional Georgian as well as other diets switch those humoral and pathophysiological mechanisms that can lead to the development of certain type of hypertension in salt-sensitive individuals. Salt intake reduction can prevent development of hypertension in salt-sensitive subjects, although hypertension develops in the salt-resistant individuals but by other mechanism such as RAAS (9). 

In many epidemiologic, clinical, and experimental studies, dietary sodium intake has been linked to blood pressure, and a reduction in dietary salt intake has been documented to lower blood pressure. In young subjects, salt intake has a programming effect in that blood pressure remains elevated even after a high salt intake has been reduced. Elderly subjects, African Americans, and obese patients are more sensitive to the blood pressure-lowering effects of a decreased salt intake. Depending on the baseline blood pressure and degree of salt intake reduction, systolic blood pressure can be lowered by 4 to 8 mm Hg. A greater decrease in blood pressure is achieved when a reduced salt intake is combined with other lifestyle interventions, such as adherence to Dietary Approaches to Stop Hypertension. A high salt intake has been shown to increase not only blood pressure but also the risk of stroke, left ventricular hypertrophy, and proteinuria. Adverse effects associated with salt intake reduction, unless excessive, seem to be minimal. However, data linking a decreased salt intake to a decrease in morbidity and mortality in hypertensive patients are not unanimous. Dietary salt intake reduction can delay or prevent the incidence of antihypertensive therapy, can facilitate blood pressure reduction in hypertensive patients receiving medical therapy, and may represent a simple cost-saving mediator to reduce cardiovascular morbidity and mortality (10).

Salt and obesity

Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase–fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome (11).

High salt intake is the major cause of raised blood pressure and accordingly leads to cardiovascular diseases. Recently, it has been shown that high salt intake is associated with an increased risk of obesity through sugar-sweetened beverage consumption. Increasing evidence also suggests a direct link. This study aimed to determine whether there was a direct association between salt intake and obesity independent of energy intake. We analyzed the data from the rolling cross-sectional study-the UK National Diet and Nutrition Survey 2008/2009 to 2011/2012. We included 458 children (52% boys; age, 10±4 years) and 785 adults (47% men; age, 49±17 years) who had complete 24-hour urine collections. Energy intake was calculated from 4-day diary and misreporting was assessed by Goldberg method. The results showed that salt intake as measured by 24-hour urinary sodium was higher in overweight and obese individuals. A 1-g/d increase in salt intake was associated with an increase in the risk of obesity by 28% (odds ratio, 1.28; 95% confidence interval, 1.12-1.45; P=0.0002) in children and 26% (odds ratio, 1.26; 95% confidence interval, 1.16-1.37; P<0.0001) in adults, after adjusting for age, sex, ethnic group, household income, physical activity, energy intake, and diet misreporting, and in adults with additional adjustment for education, smoking, and alcohol consumption. Higher salt intake was also significantly related to higher body fat mass in both children (P=0.001) and adults (P=0.001) after adjusting for age, sex, ethnic group, and energy intake. These results suggest that salt intake is a potential risk factor for obesity independent of energy intake (12).

 Salt and osteoporosis

 Osteoporosis, main risk factor for suffering fragility fractures, is an important public health problem which has undoubted social, health and economic impact; but mainly causes pain, functional limitation and severe alterations in the patient's quality of life. Its current prevalence is very high and a further increase is expected due to a higher life expectancy and the progressive ageing of the population. In the prevention of osteoporosis, the main goal is to prevent fragility fractures; for this reason, it is necessary to: 

• promote bone formation in youth, to get sufficient bone mass peak 
• reduce bone loss in adulthood, especially after menopause
• maintain bone health throughout life
• prevent falls 

There is enough evidence that multifactorial strategies (assessment of risk factors, healthy lifestyle habits, smoking cessation, moderation in alcohol consumption, physical exercise, outdoor activity with prudent exposure to sunlight, and a varied and balanced diet), are effective in the population at risk. Regarding factors for the prevention of osteoporosis, current recommendations are: increased consumption of calcium, phosphorus, magnesium and fluoride; provide adequate vitamin D (even with fortified food if necessary); consumption of foods rich in omega-3 acids; reduction of salt and prepared ready meals; sufficient but moderate intake of protein and, in the absence of intolerance, promote the consumption of milk and dairy products, especially yogurt and fermented milk products (13).

Salt and other risk factors

Consumption of fructose has increased during the last 50 years. Excessive fructose consumption has a detrimental effect on mammalian health but the mechanisms remain unclear. In humans, a direct relationship exists between dietary intake of added sugars and increased risk for cardiovascular disease mortality. While the causes for this are unclear, we recently showed that fructose provided in the drinking water induces a salt-dependent increase in blood pressure in Sprague-Dawley rats in a matter of days. However, little is known about the effects of fructose in renal salt handling and whether combined intake of high fructose and salt can lead to salt-sensitive hypertension before the development of metabolic abnormalities. The long-term (more than 4 wk) adverse effects of fructose intake on renal function are not just due to fructose but are also secondary to alterations in metabolism which may have an impact on renal function. This minireview focuses on the acute effect of fructose intake and its effect on salt regulation, as they affect blood pressure (14).

Both dietary salt and sugar are related to blood pressure (BP). The evidence for salt is much stronger, and various types of studies have consistently shown that salt is a major cause of raised BP, and a reduction from the current intake of ≈ 9-12 g/day in most countries of the world to the recommended level of 5-6 g/day lowers BP in both hypertensive and normotensive individuals, in men and women, in all age groups and in all ethnic groups. Countries such as Finland and the UK that have successfully reduced salt intake have demonstrated a reduction in population BP and cardiovascular mortality, with major cost savings to the health service. The mechanisms whereby salt raises BP are not fully understood. The traditional concepts focus on the tendency for an increase in extracellular fluid volume. Increasing evidence suggests that small increases in plasma sodium may play an important role. There are several other factors that also increase BP, one of which is added sugars. The current high intake of added sugars increases obesity which, in turn, raises BP. Recent studies also suggest that added sugars, particularly those in soft drinks, may have a direct effect on BP. However, the relationship between soft drink consumption and BP could be, at least partially, mediated by the effect of salt intake on increasing soft drink consumption. Actions to reduce salt and sugar intake across the whole population will have major beneficial effects on health along with major cost savings (15).

References________________________________

(1) Obesity and overweight fact sheet number 311. Updated June 2016. Geneva: World Health Organization, 2015.

(2) Sodium intake and blood pressure in children with clinical conditions: A systematic review with meta-analysis.  Rios-Leyvraz M, Bloetzer C, Chatelan A, Bochud M, Burnier M, Santschi V, Paradis G, Tabin R, Bovet P, Chiolero A.  J Clin Hypertens (Greenwich). 2018 Nov 29. doi: 10.1111/jch.13436.

(3) Salt intake in children and its consequences on blood pressure.  Lava SA, Bianchetti MG, Simonetti GD.  Pediatr Nephrol. 2015 Sep;30(9):1389-96. doi: 10.1007/s00467-014-2931-3.

(4) Effects of dietary sodium on metabolites: the Dietary Approaches to Stop Hypertension (DASH)–Sodium Feeding Study  Andriy Derkach, Joshua Sampson, Justin Joseph, Mary C Playdon and Rachael  Stolzenberg-Solomon  Am J Clin Nutr. 2017 Oct; 106(4): 1131–1141.  Published online 2017 Aug 30. doi:  [10.3945/ajcn.116.150136]

(5) Reported high salt intake is associated with increased prevalence of abdominal aortic aneurysm and larger aortic diameter in older men.  Golledge J, Hankey GJ, Yeap BB, Almeida OP, Flicker L, Norman PE.  PLoS One. 2014 Jul 18;9(7):e102578. doi: 10.1371/journal.pone.0102578.

(6) High and Low Salt Intake during Pregnancy: Impact on Cardiac and Renal Structure in Newborns.  Seravalli P, de Oliveira IB, Zago BC, de Castro I, Veras MM, Alves-Rodrigues EN, Heimann JC.  PLoS One. 2016 Aug 25;11(8):e0161598. doi: 10.1371/journal.pone.0161598. 

(7) Changes in the renin-angiotensin-aldosterone system in response to dietary salt intake in normal and hypertensive pregnancy. A randomized trial.  Nielsen LH, Ovesen P, Hansen MR, Brantlov S, Jespersen B, Bie P, Jensen BL.  J Am Soc Hypertens. 2016 Nov;10(11):881-890.e4. doi: 10.1016/j.jash.2016.10.001. 

(8) Is Salt a Culprit or an Innocent Bystander in Hypertension? A Hypothesis Challenging the Ancient Paradigm.  DiNicolantonio JJ, Mehta V, O'Keefe JH.  Am J Med. 2017 Aug;130(8):893-899. doi: 10.1016/j.amjmed.2017.03.011.

(9) Possible mechanism of development of salt sensitive essential Hypertension  Kantaria N, Pantsulaia I, Andronikashvili I, Simonia G.  Georgian Med News. 2016 Sep;(258):28-32.

(10) Salt and hypertension: is salt dietary reduction worth the effort?  Frisoli TM, Schmieder RE, Grodzicki T, Messerli FH.  Am J Med. 2012 May;125(5):433-9. doi: 10.1016/j.amjmed.2011.10.023. Review. Erratum in: Am J Med. 2012 Oct;125(10):e27.

(11) High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism.  Lanaspa MA, Kuwabara M, Andres-Hernando A, Li N, Cicerchi C, Jensen T, Orlicky DJ, Roncal-Jimenez CA, Ishimoto T, Nakagawa T, Rodriguez-Iturbe B, MacLean PS, Johnson RJ.  Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):3138-3143. doi: 10.1073/pnas.1713837115. Epub 2018 Mar 5. Erratum in: Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9509.

(12) High salt intake: independent risk factor for obesity?  Ma Y, He FJ, MacGregor GA.  Hypertension. 2015 Oct;66(4):843-9. doi: 10.1161/HYPERTENSIONAHA.115.05948. 

(13) Nutritional factors in preventing osteoporosis.  Martín Jiménez JA, Consuegra Moya B, Martín Jiménez MT. Nutr Hosp. 2015 Jul 18;32 Suppl 1:49-55. doi: 10.3305/nh.2015.32.sup1.9480. Spanish.

(14) Direct renal effects of a fructose-enriched diet: interaction with high salt intake.  Ares GR, Ortiz PA.  Am J Physiol Regul Integr Comp Physiol. 2015 Nov 1;309(9):R1078-81. doi: 10.1152/ajpregu.00156.2015. 

(15) Salt and sugar: their effects on blood pressure.  He FJ, MacGregor GA Pflugers Arch. 2015 Mar;467(3):577-86. doi: 10.1007/s00424-014-1677-x.