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Is Salt a Culprit or an Innocent Bystander in Hypertension? A Hypothesis Challenging the Ancient Paradigm

      Abstract

      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.

      Keywords

      Clinical Significance
      • There is no definitive proof that a normal salt intake causes hypertension.
      • The evidence in the literature suggests that sugar, not salt, is the principal driver of hypertension and cardiovascular disease.
      Hypertension is defined by a systolic blood pressure that is ≥140 mm Hg and a diastolic blood pressure that is ≥90 mm Hg.
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      Long-term high salt diet causes hypertension and decreases renal expression of vascular endothelial growth factor in Sprague-Dawley rats.
      In recent decades hypertension has been ranked as one of the leading causes of worldwide disability-adjusted life years.
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      According to a study conducted by Kearney et al,
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      more than 1 billion adults worldwide (approximately 25%) have hypertension. Other estimates suggest this number will climb to 29% by 2025.
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      In the literature it is often said that an excessive intake of salt (NaCl) can lead to hypertension.
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      In general, the average daily salt intake is more than 6 g (2400 mg of sodium), with approximately 95% of the global population consuming somewhere between 7.5 and 12.5 g of salt.
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      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      Some European and Asian countries consume slightly more than 12 g of salt (4800 mg of sodium) per day.
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      In India most people consume at least 11 g of salt per day,
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      • et al.
      Mean population salt consumption in India: a systematic review.
      but this may have to do with the hot climate of India, which can induce salt loss of up to 6 g per day (mostly from sweat).
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      Salt restriction in hypertension.
      Despite these important nuances, various government institutions and bodies recommend population-wide sodium restriction.
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      US Department of Agriculture and US Department of Health and Human Services
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      The World Health Organization (WHO) recommends an intake of <2000 mg sodium per day.
      World Health Organization
      Diet, Nutrition, and the Prevention of Chronic Diseases. Report of a Joint WHO/FAO Study Group.
      Canada's 2010 Sodium Working Group suggest sodium intake of <2300 mg/d,
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      whereas the American Heart Association suggests an even stricter sodium intake (<1500 mg/d).
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      Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond.
      The recently published 2015 Dietary Guidelines for Americans recommend a sodium restriction of <2300 mg/d.
      US Department of Agriculture and US Department of Health and Human Services
      Dietary Guidelines for Americans, 2015-2020.
      The Food and Agricultural Organisation of the United Nations has published food-dietary guidelines for Indians, which suggested that the salt intake should be <2400 mg/d.
      National Institute of Nutrition
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      India, along with other member states of the WHO, has adopted a target of reducing the mean population salt consumption up to 30% by 2025.
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      • et al.
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      This reduction in salt intake is targeted with a belief that this will lead to a decrease in blood pressure levels, with the assumption that this will translate into a reduction in cardiovascular events.
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      • Li J.
      • Macgregor G.A.
      Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials.
      Previously, on the basis of a meta-analysis, it was suggested that a reduction in dietary salt intake of up to 6 g per day could help reduce the systolic/diastolic blood pressure by 7/4 mm Hg in hypertensives and 4/2 mm Hg in normotensives.
      • He F.J.
      • Li J.
      • Macgregor G.A.
      Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials.
      However, recently, DiNicolantonio et al
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      have proposed the idea that added sugars, not salt, is the real culprit for causing hypertension.
      If this hypothesis is proved to be correct, then it would be a great relief for the entire population, especially cultures that rely on saltier dishes (such as the Indian population), probably helping them to prevent dehydration in the heat.
      • Ghooi R.B.
      • Valanju V.V.
      • Rajarshi M.G.
      Salt restriction in hypertension.
      The present article reviews the literature and hypothesizes that 1) salt intake not may not be an important etiologic factor for hypertension; 2) salt restriction paradoxically may cause hypertension and cardiovascular events; and 3) dietary sugar is the more problematic white crystal inducing hypertension.

      Hypertension in the Indian Population

      Hypertension is a serious public health threat on healthcare systems and cardiovascular health status in India.
      Trustees of Columbia University in the City of New York
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      Responding to the threat of chronic diseases in India.
      Twenty-four percent of all coronary heart disease and 57% of all stroke deaths in India are attributed to hypertension.
      • Gupta R.
      Trends in hypertension epidemiology in India.
      According to the 2008 WHO estimates, the prevalence rate of hypertension in the Indian population was 32.5% (33.2% in men and 31.7% in women).
      World Health Organization
      Noncommunicable diseases country profiles (India).
      The studies, including the 2005 Global Burden of Hypertension,
      • Kearney P.M.
      • Whelton M.
      • Reynolds K.
      • Muntner P.
      • Whelton P.K.
      • He J.
      Global burden of hypertension: analysis of worldwide data.
      the 2010 Global Burden of Disease,
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      • et al.
      A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
      and the 2011 WHO Noncommunicable Diseases India-specific data,
      World Health Organization
      Noncommunicable diseases country profiles (India).
      showed an alarming rise in hypertension in the Indian population.
      The prevalence rate of hypertension in India has been approximately 25% in urban areas and 10% in rural areas, according to recent studies.
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      Prevalence-correlates-awareness-treatment and control of hypertension in Kumarakom, Kerala: baseline results of a community-based intervention program.
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      Hence, to curb this deadly disease, the Indian Government has started the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke for prevention and control of disease at the root cause.
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      National Health Programs of India: National Policies & Legislations Related to Health.

      Why Has Hypertension Been on the Rise in India?

      The consumption of added sugars may be a culprit driving the increased prevalence of hypertension in India. Other risk factors include age, race, family history, tobacco, alcohol, a low potassium intake, vitamin D deficiency, stress, and high salt diet.

      Staff MC. High blood pressure (hypertension) - Risk Factors. Diseases and Conditions, CON-20019580. Available at: http://www.mayoclinic.org/diseases-conditions/high-blood-pressure/basics/risk-factors/con-20019580. Accessed December 14, 2016.

      However, salt may simply come along with more added sugars; in other words, salt may be an “innocent bystander” rather than a causative agent in hypertension.

      Can Low-salt Diets Cause Hypertension, Cardiovascular Events, and Other Unintended Consequences?

      In the last 4 to 5 decades, patients with hypertension were given advice to cut down their intake of salt and increase exercise. Yet these recommendations are contradictory, because exercise or physical work (particularly when done in a warm or hot environment) on a low-salt diet causes a 10-fold increased risk of heat exhaustion and prostration (characterized by nausea, vomiting, tachycardia, hypotension, vertigo, dehydration, and collapse).
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      • Keys A.
      The effect of sodium chloride intake on the work performance of man.
      Moreover, following the advice to consume <2300 mg of sodium per day can lead to negative sodium balance, as well as negative calcium and magnesium balance.
      • Kodama N.
      • Nishimuta M.
      • Suzuki K.
      Negative balance of calcium and magnesium under relatively low sodium intake in humans.
      Thus, low-salt diets may predispose to calcium and magnesium deficiency and all the negative consequences that come with it (including osteoporosis, hypertension, cardiovascular events, arrhythmias, coronary vasospasm, sudden death, and more). Furthermore, recent studies suggest that sugar, not salt, is the likely dietary culprit causing hypertension.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.

      Assumed Pathophysiology Behind Salt-induced Hypertension

      One of the first and most comprehensive explanations around the association between salt intake and hypertension was given by Guyton et al.
      • Guyton A.C.
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      • Cowley Jr., A.V.
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      • Manning Jr., R.D.
      • Norman Jr., R.A.
      Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension.
      They suggested that sodium balance is regulated by the pressure-natriuresis mechanism. Sodium loading was found to be associated with an increase in blood pressure levels, which returned to previous values after regulation of extracellular volume and pressure-natriuresis. However, some individuals have difficulties in eliminating excess sodium, and for the same pressure-natriuresis effect they need to have higher blood pressure, potentially leading to more chronic expansions of extracellular volume, followed by higher cardiac output with tissue perfusion that exceeds metabolic needs. Peripheral tissue vasculature counteracts by activating auto-regulatory vasoconstriction, leading to an increase in peripheral resistance.
      • Guyton A.C.
      • Coleman T.G.
      • Cowley Jr., A.V.
      • Scheel K.W.
      • Manning Jr., R.D.
      • Norman Jr., R.A.
      Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension.
      • Guyton A.C.
      Blood pressure control–special role of the kidneys and body fluids.
      However, the fact that some people tolerate dietary sodium whereas others do not suggests that an underlying factor that is independent of dietary sodium causes “salt-sensitive” hypertension. Interestingly, the renin–angiotensin–aldosterone system (RAAS) plays a major role in regulating sodium–blood pressure response, and dietary sugar (fructose in particular) seems to affect the kidneys in a way that creates salt-sensitive hypertension.
      • Rodriguez-Iturbe B.
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      Salt-sensitive hypertension–update on novel findings.
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      Dietary fructose and hypertension.

      Can Salt Cause Hypertension?

      The human brain (hypothalamus) is wired to maintain salt (sodium) balance and hence controls our salt intake.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      • Denton D.A.
      • McKinley M.J.
      • Weisinger R.S.
      Hypothalamic integration of body fluid regulation.
      • Tekol Y.
      Salt addiction: a different kind of drug addiction.
      The biological reason behind this tight homeostatic regulation is that the maintenance of normal sodium levels in the extracellular fluid is required for life and for cellular processes to function properly. The transition process from marine milieu to land-based existence required the evolution of cells that were able to simulate the salty environment of their progenitor cells that existed in sea water. Our remote prehuman hominin ancestors were probably mostly vegetarian (with a diet consisting of, eg, plants, herbs, fruits, and nuts) that were low in sodium.
      • Cirillo M.
      • Capasso G.
      • Di Leo V.A.
      • De Santo N.G.
      A history of salt.
      • Denton D.A.
      The Hunger for Salt: An Anthropological, Physiological and Medical Analysis.
      However, these early hominins were likely consuming insects, organs, blood, and other animal-based foods when available, which will dramatically increase the overall salt intake. Additionally, salt was considered the essence of life, and if anything was eaten without salt, it was considered to lack an essential element.
      • Cirillo M.
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      • De Santo N.G.
      A history of salt.

      Plutarch. Moralia. Clement PA, Hoffleit HB, trans. Volume VIII table-talk, books 1-6. Loeb Classical Library 424. Boston: Harvard University Press; 1969.

      • Lapicque L.
      Documents ethnographiques sur l' alimentation minérale.
      Hence, sodium was an important factor that was conserved in our body with the help of our brain and kidneys. Extracellular fluids had to be kept sodium-rich, whereas intracellular fluids had to be kept relatively free of sodium, allowing cellular and vascular volumes to be maintained. Hence, when sodium levels are low, blood volume is low, which signals the body to ingest more salt and water.
      • Denton D.A.
      • McKinley M.J.
      • Weisinger R.S.
      Hypothalamic integration of body fluid regulation.
      Interestingly, in hot tropical countries adequate salt intake was necessary to acclimate to the salt loss through sweat, leading to a higher salt intake.
      • Cirillo M.
      • Capasso G.
      • Di Leo V.A.
      • De Santo N.G.
      A history of salt.
      In other words, bodily need drives salt intake. In fact, the low-salt advice may lead to salt cravings and an overconsumption of more processed foods to obtain the salt our physiology desires.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      However, nowadays, to get the salt our body needs we end up consuming salty processed foods (instead of naturally salty foods) and thus consume a greater amount of harmful dietary substances (eg, excess calories, added sugars, harmful fats, and artificial flavorings).
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      Indeed, low-salt diets may inadvertently cause us to eat more added sugars. When we are deficient in salt there is an enhanced craving for it, but this does not mean we are addicted to salt.
      • Denton D.A.
      • McKinley M.J.
      • Weisinger R.S.
      Hypothalamic integration of body fluid regulation.
      • Tekol Y.
      Salt addiction: a different kind of drug addiction.
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      Microdialysis studies of brain norepinephrine, serotonin, and dopamine release during ingestive behavior. Theoretical and clinical implications.
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      Salt craving: the psychobiology of pathogenic sodium intake.

      Salt: The Ancient Crystal that Allows Increased Consumption of Vegetables

      According to the Salted Food Addition Hypothesis, if salted foods are consumed daily this can lead to salted food addiction. However, if this were true the intake of salt would be increasing rather than remaining in a biologically determined narrow range, which has occurred throughout numerous countries over the last 50 or more years.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      Despite this overlooked issue with the hypothesis, many still believe that salting foods can lead to overeating and its related complications.
      • Cocores J.A.
      • Gold M.S.
      The Salted Food Addiction Hypothesis may explain overeating and the obesity epidemic.
      What is overlooked is that adding salt to bitter or bland foods, like vegetables or nuts, will probably increase their consumption because salt enhances flavor. Moreover, a higher intake of vegetables and nuts for example, is associated with a reduction in the risk for hypertension and cardiovascular events.
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      • et al.
      A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group.
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      Olive oil, the Mediterranean diet, and arterial blood pressure: the Greek European Prospective Investigation into Cancer and Nutrition (EPIC) study.
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      • et al.
      Critical review: vegetables and fruit in the prevention of chronic diseases.
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      Dietary patterns associated with hypertension prevalence in the Cameroon defence forces.
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      Regular consumption of nuts is associated with a lower risk of cardiovascular disease in women with type 2 diabetes.
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      Health benefits of nut consumption.
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      • Rudich T.
      • Gaziano J.M.
      Nut consumption and risk of hypertension in US male physicians.
      Salt (sodium) “appetite” is an evolutionary conserved mechanism that is approximately 100 million years old.
      • Liedtke W.B.
      • McKinley M.J.
      • Walker L.L.
      • et al.
      Relation of addiction genes to hypothalamic gene changes subserving genesis and gratification of a classic instinct, sodium appetite.
      It drives us to seek out and obtain salt when we need it.
      • Denton D.A.
      • McKinley M.J.
      • Weisinger R.S.
      Hypothalamic integration of body fluid regulation.
      An intake of sodium between 3000 and 5000 mg/d also helps to keep the RAAS and sympathetic nervous system (ie, noradrenaline and adrenaline) suppressed, which places the least amount of stress on bodily organs.
      • DiNicolantonio J.J.
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      • Sadaf R.
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      • Lucan S.C.
      • Lavie C.J.
      Dietary sodium restriction: take it with a grain of salt.
      • Heaney R.P.
      Making sense of the science of sodium.
      In short, a person's salt intake is controlled by need but also to ensure homeostasis.

      Salt Restriction Can Lead to Insulin Resistance

      Physicians around the world generally ask hypertension patients to restrict salt intake, without being aware of the unintended consequences. Salt restriction has been observed to cause an increase in insulin (hyperinsulinemia) and C-peptide levels,
      • Fliser D.
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      Serum lipid changes on low salt diet. Effects of alpha 1-adrenergic blockade.
      • da Costa Lima N.K.
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      • dos Santos E.A.
      • et al.
      Chronic salt overload increases blood pressure and improves glucose metabolism without changing insulin sensitivity.
      • Patel S.M.
      • Cobb P.
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      • Zhang X.
      • de Jesus J.M.
      • Cogswell M.E.
      Dietary sodium reduction does not affect circulating glucose concentrations in fasting children or adults: findings from a systematic review and meta-analysis.
      which can worsen insulin resistance.
      • Sharma A.M.
      • Arntz H.R.
      • Kribben A.
      • Schattenfroh S.
      • Distler A.
      Dietary sodium restriction: adverse effect on plasma lipids.
      However, the increase in insulin levels on low-salt diets could be due to a reduced insulin-independent clearance of glucose or due to the higher angiotensin-II levels that can lead to a decrease in blood flow to the liver, which is responsible in clearing insulin from the blood stream.
      • da Costa Lima N.K.
      • Lima F.B.
      • dos Santos E.A.
      • et al.
      Chronic salt overload increases blood pressure and improves glucose metabolism without changing insulin sensitivity.
      • Peiris A.N.
      • Mueller R.A.
      • Smith G.A.
      • Struve M.F.
      • Kissebah A.H.
      Splanchnic insulin metabolism in obesity. Influence of body fat distribution.
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      • Mottram F.R.
      • et al.
      The action of angiotensin in man.
      Regardless, the increase in insulin levels caused by insulin resistance can lead to increased fat mass accumulation and obesity, causing hypertension.
      It was also observed that a high-salt diet stimulates insulin-independent glucose uptake without interfering with insulin sensitivity,
      • Egan B.M.
      • Stepniakowski K.
      Effects of enalapril on the hyperinsulinemic response to severe salt restriction in obese young men with mild systemic hypertension.
      which can be due to an increase in number of glucose transporters (GLUT-1, GLUT-4, or both) in adipocytes because of a high-salt diet.
      • da Costa Lima N.K.
      • Lima F.B.
      • dos Santos E.A.
      • et al.
      Chronic salt overload increases blood pressure and improves glucose metabolism without changing insulin sensitivity.
      Hence, a high-salt diet can induce protection from the harmful effects of a diet high in sugar, which is the likely primary dietary culprit behind obesity, atherosclerosis, and subsequently hypertension.

      Does a High-salt Diet Cause Fluid Overload?

      DiNicolantonio et al
      • DiNicolantonio J.J.
      • O'Keefe J.H.
      Hypertension due to toxic white crystals in the diet: should we blame salt or sugar?.
      have revealed how an overconsumption of added sugars can lead to fluid and salt overload, whereas dietary salt is more of an innocent bystander in this phenomenon.
      • DiNicolantonio J.J.
      • O'Keefe J.H.
      Hypertension due to toxic white crystals in the diet: should we blame salt or sugar?.
      It is observed that most patients with essential hypertension have normal blood volume and body sodium but an increase in peripheral vascular resistance.
      • Perera G.A.
      • Blood D.W.
      The relationship of sodium chloride to hypertension.
      • Pines K.L.
      • Perera G.A.
      Sodium chloride restriction in hypertensive vascular disease.
      However, salt restriction may worsen peripheral vascular resistance, and consuming normal salt intakes, as compared with low-salt intakes, may actually improve peripheral vascular resistance,
      • Omvik P.
      • Lund-Johansen P.
      Hemodynamic effects at rest and during exercise of long-term sodium restriction in mild essential hypertension.
      suggesting that salt may not be an etiologic factor for hypertension.
      Moreover, diets high in salt do not seem to lead to an overall rise in total body water content.
      • Heer M.
      • Baisch F.
      • Kropp J.
      • Gerzer R.
      • Drummer C.
      High dietary sodium chloride consumption may not induce body fluid retention in humans.
      Additionally, serum sodium levels are infrequently found to be high, whereas a low-sodium level is a very common electrolyte abnormality in both the inpatient and outpatient setting, which suggests that some patients may indeed benefit from consuming more salt rather than less. Perhaps more importantly, 80 million Americans are now prediabetic, and another 20 million have type 2 diabetes. In fact, abnormal glucose homeostasis and elevated serum glucose levels (generally from decades of consuming diets high in added sugars and other refined carbohydrates) are one of the most pressing public health concerns worldwide. Chronically elevated glucose levels can lead to an increase in inflow of water from tissue cells to the intravascular space, leading to an increase in intravascular volume, which if not compensated for, may lead to hypertension.
      • Palmer B.F.
      • Clegg D.J.
      Electrolyte and acid-base disturbances in patients with diabetes mellitus.
      In addition, an overconsumption of added sugars/refined carbohydrates has been shown to reduce nitric oxide (possibly leading to increased peripheral vascular resistance), increased oxidative stress, activation of the RAAS, and increased insulin levels—all of which sets the stage for chronic elevations in blood pressure.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.

      Added Sugars and Hypertension

      Certain evidence suggests that added sugars, not salt, may be a dietary culprit for causing hypertension.
      • DiNicolantonio J.J.
      • O'Keefe J.H.
      Hypertension due to toxic white crystals in the diet: should we blame salt or sugar?.
      Antar et al
      • Antar M.A.
      • Ohlson M.A.
      • Hodges R.E.
      Changes in retail market food supplies in the United States in the last seventy years in relation to the incidence of coronary heart disease, with special reference to dietary carbohydrates and essential fatty acids.
      concluded that 56% of nondiabetic patients with arteriosclerosis have abnormal glucose tolerance, linking elevated glucose levels with atherosclerosis. They found that a diet high in sugar leads to an increase in the level of all major fractions of serum lipids.
      • Antar M.A.
      • Ohlson M.A.
      • Hodges R.E.
      Changes in retail market food supplies in the United States in the last seventy years in relation to the incidence of coronary heart disease, with special reference to dietary carbohydrates and essential fatty acids.
      One study concluded that “…modest intake of dietary sucrose is associated with cardiovascular adaptations that may further burden a heart already compromised by the presence of systemic hypertension.”
      • Brown C.M.
      • Dulloo A.G.
      • Yepuri G.
      • Montani J.P.
      Fructose ingestion acutely elevates blood pressure in healthy young humans.
      In other words, overconsuming added sugars may not only lead to hypertension but also to cardiovascular disease.
      Daily consumption of fruit juice (composed mainly of free sugars) is also associated with a higher central blood pressure.
      • Pase M.P.
      • Grima N.
      • Cockerell R.
      • Pipingas A.
      Habitual intake of fruit juice predicts central blood pressure.
      Animal and human studies show that a diet high in sucrose or fructose can increase blood pressure.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      • Hwang I.S.
      • Ho H.
      • Hoffman B.B.
      • Reaven G.M.
      Fructose-induced insulin resistance and hypertension in rats.
      • Hwang I.S.
      • Huang W.C.
      • Wu J.N.
      • Shian L.R.
      • Reaven G.M.
      Effect of fructose-induced hypertension on the renin-angiotensin-aldosterone system and atrial natriuretic factor.
      • Srinivasan S.R.
      • Berenson G.S.
      • Radhakrishnamurthy B.
      • Dalferes Jr., E.R.
      • Underwood D.
      • Foster T.A.
      Effects of dietary sodium and sucrose on the induction of hypertension in spider monkeys.
      Perhaps the best evidence comes from a meta-analysis of randomized, controlled trials that showed that a diet high in sugar, as compared with a low-sugar diet, for just a few weeks causes an increase in blood pressure of approximately 7.6/6.1 mm Hg.
      • Te Morenga L.A.
      • Howatson A.J.
      • Jones R.M.
      • Mann J.
      Dietary sugars and cardiometabolic risk: systematic review and meta-analyses of randomized controlled trials of the effects on blood pressure and lipids.
      Hence, a diet high in added sugars leads to numerous metabolic disturbances, reflected by hyperlipidemia, fluid overload, insulin resistance, and hypertension.

      High-salt Diets Alone Are Unlikely to Cause Hypertension

      Dietary salt has been considered as one of the most important etiologic causes of hypertension. However, according to a study conducted by Hall,
      • Hall J.E.
      Guyton and Hall Textbook of Medical Physiology.
      increasing salt intake in individuals with normal kidney function “usually does not increase arterial pressure much because the kidneys rapidly eliminate the excess salt and blood volume is hardly altered.” Other studies also mention the same principal, saying that individuals with normal kidney functions eliminate excess dietary salt with ease.
      • Lifton R.P.
      • Gharavi A.G.
      • Geller D.S.
      Molecular mechanisms of human hypertension.
      • Cruz D.N.
      • Simon D.B.
      • Nelson-Williams C.
      • et al.
      Mutations in the Na-Cl cotransporter reduce blood pressure in humans.
      • Brands M.W.
      Chronic blood pressure control.
      • Guyton A.C.
      Long-term arterial pressure control: an analysis from animal experiments and computer and graphic models.
      In the 20th century, Allen and Sherrill conducted a study and observed that prolonged blood pressure reduction was seen in only 60% of 180 patients with hypertension when salt intake was restricted to less than 2 g per day. However, they did not find any significant increase in blood pressure when the individuals were administered 10-20 g of salt for 2 weeks in 3 patients with normal blood pressure.
      • Pines K.L.
      • Perera G.A.
      Sodium chloride restriction in hypertensive vascular disease.
      Other studies were conducted that showed similar results.
      • Grant H.
      • Reischsman F.
      The effects of the ingestion of large amounts of sodium chloride on the arterial and venous pressures of normal subjects.
      • Berger S.S.
      • Fineberg M.H.
      The effect of sodium chloride on hypertension.
      Kawasaki et al
      • Kawasaki T.
      • Delea C.S.
      • Bartter F.C.
      • Smith H.
      The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension.
      further stated that “Salt loading alone or with injection of desoxycorticosterone acetate (DOCA) virtually never increases blood pressure significantly in normal subjects.”
      In contrast, studies even suggest that higher salt loads can decrease blood pressure.
      • Omvik P.
      • Gerdts E.
      • Myking O.
      • Lund-Johansen P.
      Similar central hemodynamics in salt-sensitive and salt-resistant hypertensive patients.
      Luft et al
      • Luft F.C.
      • Rankin L.I.
      • Henry D.P.
      • et al.
      Plasma and urinary norepinephrine values at extremes of sodium intake in normal man.
      suggested that “sympathetic nervous system activity appears to decrease with sodium loading in normal subjects. These responses may have facilitated the excretion of massive salt loads in normal subjects and may have modulated the increases in blood pressure.” Low-salt diets can also lead to vasoconstriction,
      • Sullivan J.M.
      • Ratts T.E.
      • Taylor J.C.
      • et al.
      Hemodynamic effects of dietary sodium in man: a preliminary report.
      and consuming more salt in normotensives can lead to vasodilatation.
      • Egan B.M.
      • Weder A.B.
      • Petrin J.
      • Hoffman R.G.
      Neurohumoral and metabolic effects of short-term dietary salt restriction in men. Relationship to salt-sensitivity status.
      High-salt diets have also been blamed for increasing serum sodium levels, causing chronic volume retention and hypertension.
      • He F.J.
      • Markandu N.D.
      • Sagnella G.A.
      • de Wardener H.E.
      • MacGregor G.A.
      Plasma sodium: ignored and underestimated.
      However, studies fail to show that patients with hypertension have an increase in extracellular volume. Surprisingly, elevations in extracellular concentrations of sodium, even for 6 days, are unable to increase blood pressure in animals.
      • Haddy F.J.
      • Scott J.B.
      The mechanism of the acute effect of sodium chloride on blood pressure.
      • Norman Jr., R.A.
      • Coleman T.G.
      • Wiley Jr., T.L.
      • Manning Jr., R.D.
      • Guyton A.C.
      Separate roles of sodium ion concentration and fluid volumes in salt-loading hypertension in sheep.
      Moreover, a higher-salt diet does not seem to lead to over-retention of water.
      • Heer M.
      • Baisch F.
      • Kropp J.
      • Gerzer R.
      • Drummer C.
      High dietary sodium chloride consumption may not induce body fluid retention in humans.
      • Omvik P.
      • Lund-Johansen P.
      Is sodium restriction effective treatment of borderline and mild essential hypertension? A long-term haemodynamic study at rest and during exercise.
      Most importantly, a meta-analysis of almost 170 studies noted that sodium restriction only lowers blood pressure by approximately 1%-3% in normotensives and 3.5%-7% in hypertensives
      • Graudal N.A.
      • Hubeck-Graudal T.
      • Jurgens G.
      Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.
      ; however, restricting sodium increases aldosterone, renin, noradrenaline, and blood lipids. It is hard to justify dietary sodium restriction when the overall cardiovascular risk seems to worsen rather than improve when all risk factors are taken into account.
      Hence, the overall evidence in the literature suggests that salt is not the primary culprit but an innocent bystander in hypertension. There is no proof that the potential benefits of dietary salt restriction outweigh the risks. The hypothesis that sodium restriction may lead to hypertension, obesity, type 2 diabetes, and cardiovascular disease is depicted in Figure.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.
      Figure thumbnail gr1
      FigureHow sodium restriction may lead to hypertension, obesity, type 2 diabetes, and cardiovascular disease.
      • DiNicolantonio J.J.
      • Lucan S.C.
      The wrong white crystals: not salt but sugar as aetiological in hypertension and cardiometabolic disease.

      Conclusion

      The cumulative body of evidence suggests that the overconsumption of salt is not the primary cause of hypertension, whereas added sugars are more likely the true culprit. Salt restriction may actually worsen overall cardiovascular health through numerous counter-regulatory mechanisms, and may lead to other unintended consequences (insulin resistance, type 2 diabetes, and obesity). Clinicians should advise their hypertensive patients to cut down on the intake of added sugars (sucrose and high fructose corn syrup) and refined carbohydrates such as white flour, and make dietary salt less of an issue.

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