Hypertension Journal

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Dietary Salt and Blood Pressure: Verdict is Clear,so why Any Debate?
  JOHTN
SALT AND BLOOD PRESSURE
Dietary Salt and Blood Pressure: Verdict is Clear,
so why Any Debate?
1Norm RC Campbell, 2Francesco P Cappuccio
1,2Professor
1Department of Medicine, Community Health Sciences andPhysiology and Pharmacology, O'Brien Institute of PublicHealth and Libin Cardiovascular Institute of Alberta, Universityof Calgary, Calgary, Alberta, Canada
2Department of Cardiovascular Medicine and EpidemiologyUniversity of Warwick, WHO Collaborating Centre, WarwickMedical School, Coventry, UK
Correspondence: Norm RC Campbell, ProfessorDepartment of Medicine, Community Health Sciences andPhysiology and Pharmacology, O'Brien Institute of PublicHealth and Libin Cardiovascular Institute of Alberta, Universityof Calgary, Calgary, Alberta, Canada
Phone: +4032107961
e-mail: ncampbell@ucalgary.ca
 
ABSTRACT
Repeated reviews of the evidence to produce recommendationsfor dietary salt intake have been conducted by independentcommittees of national and international scientific andgovernmental organizations. These recommendations supportreducing dietary salt to less than 6 gm/day and many to lessthan 5 gm/day. Nevertheless, there is controversy aboutrecommendations to reduce dietary salt. This commentarydiscusses low quality research studies and commercialinterests as sources of the controversy. Especially, researchthat assesses usual salt intake in individuals based on a singlespontaneously voided (spot) urine sample is discussed as aweak research method prone to erroneous findings. Further,some investigators have altered scientific formula to maketheir data using spot urine samples appear more robust andmade misleading and false statements about evidence relatingto dietary salt. Counterintuitive findings based on studies thathave used spot urine samples is frequently disregarded inexpert committee review given the low quality evidence isincompatible with higher quality evidence which shows directlinear relationships between dietary salt, hypertension andcardiovascular disease in the general population.
Keywords: Blood pressure, Cardiovascular disease, Conflictof interest, Diet, Hypertension, Nutrition, Public health, Salt,Sodium.
How to cite this article: Campbell NRC, Cappuccio FP. DietarySalt and Blood Pressure: Verdict is Clear, so why Any Debate?Hypertens J 2016;2(2):57-59.
Source of support: Nil
Conflict of interest: None
 
 
INTRODUCTION

High amount of salt/sodium in the diet is one ofthe major global health risks. The Global Burdenof Disease Study estimates 3.7 million deaths, and 74 million years of disability (DALYs) in 2013 as a resultof excess dietary salt (Institute for Health Metrics andEvaluation, 2015 University of Washington, http://vizhub.healthdata.org/gbd-compare/, accessed Feb26 2016). Multiple comprehensive reviews have beenconducted by independent national and internationalhealth and scientific organizations to develop dietarysalt recommendations, with the most recent reviewbeing conducted to support the 2015 American Dietaryrecommendations.1 These recommendations almostuniversally recommend dietary salt to be < 6 gm (< sodium2400 mg)/day or even lower, with the World HealthOrganization recommending individuals consume lessthan 5 gm salt (2000 mg sodium) per day.2 Table 1 indicatesrecommended nomenclature for describing dietary salt.

  Consistent public health recommendations are basedon extensive evidence of harm from excess dietary salt.Animal models show multiple harms from adding salt tothat naturally occurring in food, including linear increasesin blood pressure, inflammation, hypertension, directvascular, cardiac, and renal damage that are independentof blood pressure, asthma, osteoporosis, promotion ofcancer, stroke, heart failure, and premature death.2,3Hunter-gatherer populations that do not have added saltin their diets have little to no hypertension or increasein blood pressure with age and invariably consume lessthan 2.5 g salt (1000 mg sodium) per day.4 The few huntergathererpopulations with high natural sources of dietarysalt (e.g., salt in drinking water) had increases in bloodpressure and hypertension, and consumed more than 2.5 gsalt (1000 mg sodium) per day. Based on randomizedcontrolled trials of changes in dietary salt being directlyassociated with changes in blood pressure, it is estimated that over 30% of hypertension is attributed to increaseddietary salt (i.e., excess dietary salt causes more than300 million people to have hypertension globally).2 Ameta-analysis of controlled trials and several metaanalysesof higher-quality cohort studies find increaseddietary salt associated with increased cardiovasculardisease.5-7 Given the multitude of mechanisms for harm,it is not surprising that gastric cancer, renal cell cancer,asthma, adiposity, multiple sclerosis, rheumatoid arthritis,migraine, aortic aneurysm, Meniere's disease, ovariandysfunction, renal stones, and osteoporosis have beenassociated with excess dietary salt in human studies.2

Table 1: Recommended* terminology for describingdietary salt daily intake
Dietary Salt and Blood Pressure: Verdict is Clear,so why Any Debate?
*Adapted recommendations of the World Hypertension League,World Action on Salt and Health and the Australian Division ofWorld Action on Salt and Health4

Hypertension Journal, April-June, Vol 2, 2016 57

Norm RC Campbell, Francesco P Cappuccio

Nevertheless, there is still controversy about reducingdietary salt. The controversy is in part due to the resultsof flawed studies and in part due to the lack of a definitivelong-term randomized controlled trial of salt reductionand cardiovascular outcomes. However, such trialsare missing in most public health interventions withmuch less controversy. Scientists strongly feel that largeoutcome clinical trials are required to have had morethan 40 years to conduct them.

In this commentary, we provide several nonscientificsources of the controversy8 to raise further awareness ofthe covert actions that are taking place to block globalimplementation of one of the most cost-effective publichealth strategies of the century. The first is the resilientconduct and extensive promotion of low-quality researchthat is prone to erronous results. The second is potentialand real commercial conflicts of interest. The third is thelack of content knowledge about salt/public health ofdissenting scientists and the fourth is the promotion ofout of context and often misleading information.

Low-quality research can usually be exposed byexamining the study methodology.9 Criteria that havebeen used to identify high-quality research designsinclude: (1) Assessing usual dietary salt using a validmethod for at least one day and preferably multiple daysover the study duration, (2) a study duration of at least1 month when assessing changes in blood pressure andat least 1 year for assessing cardiovascular outcomes,(3) cohort studies that exclude people with disease dueto the high likelihood of reverse causality (sick peopleeat less and die more frequently), and (4) analyses incohort studies that do not adjust for blood pressure whenexamining outcomes related to salt causing increasedblood pressure. Nearly all the studies that meet thesemodest quality criteria support salt reduction and haveadequate statistical power to show harmful effects ofincreased dietary salt.6,7 The conduct of low-qualityresearch that cannot meet these modest quality criteriahave the potential to undermine the public health effortto reduce dietary salt and has led to an internationalcall for setting research standards and to the formation of an international consortium of health and scientificorganizations to set those standards.10
 
One of the best indicators of low-quality research isthe use of a single spot urine to predict long-term saltingestion in individuals. Nearly all ingested salt isexcreted within 6 hours and short-term sodium excretionis under tight regulation by a multitude of factors thatpredict cardiovascular events independent of dietarysalt (e.g., renal function, dietary potassium, sympatheticactivity, renin, angiotensin, and aldosterone). Further,the equations used to predict 24-hour urine sodiumexcretion from a spot sample have variables (e.g., age, sex,and creatinine) that predict cardiovascular disease andblood pressure independently of dietary salt. Salt intakevaries greatly "between" individuals (in a population orbetween populations). More importantly, it varies evenmore "within" the same individual from day to day.Finally, within the same day, the excretion of sodium(used as a marker of salt intake) shows a diurnal variationand it is affected by factors, such as posture, sleep-wakecycle, and neuroendocrine diurnal changes. There isno valid scientific basis for an assessment of salt intakethat lasts hours to reflect usual salt intake over a periodof years. Thus, use of a single spot urine to predict anindividual's long-term salt consumption is the "sine quanon" of low-quality research and a "sin" in salt research!

The Prospective Urban Rural Epidemiology (PURE )study is often cited as evidence that lowering dietary saltcan cause harm, but also noted to have multiple weaknesses.8 Although based on a very large internationalcohort, the PURE study assessed the usual salt intakeof individuals using a single morning spot urine sampleand related the results to both blood pressure and cardiovascularoutcomes. In assessing the association of thespot sample to 24-hour urine samples, the PURE studyalso had a multitude of issues that were likely to inflatethe association reported. Fifty percent of the 24-hoururines collected for the validation study were reportedto be incomplete. Many additional incomplete 24-hoururines were likely included because the investigatorssubstantively altered (without overt disclosure) the publishedmethod of excluding incomplete urine samples.The published formula predicting 24-hour urine sodiumfrom the spot sample had four errata. The investigatorsonly published the association of the spot sample withthe dependent 24-hour urine sample likely inflating thedegree of association by including the spot urine samplewithin the 24-hour urine sample. When requested,the investigators did not disclose the association of thespot urine sodium with the independent 24-hour urinesodium. The national population blood pressures in thePURE study are also noted to be markedly different fromthose in some high-quality national surveys conducted at the same time. The concerns about the quality of thePURE study sodium and blood pressure results makethem very difficult to interpret scientifically and hencethe results should not impact public health recommendationsto reduce dietary salt.
 
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Dietary Salt and Blood Pressure: Verdict is Clear, so why Any Debate?

Low-quality research on dietary sodium researchin our opinion should not be funded, conducted, orpublished and needs to be critiqued and discouragedduring presentations. Yet, such research is becomingvery frequent. Why? The ease of assessing sodium in aspot urine sample collected in studies not appropriatelydesigned to address salt and its health effects encouragespost-hoc analyses for studies not primarily designed toanswer the question regarding salt. Clear examples arethe PURE Study and the exploitation of datasets, such asTranscend and Ontarget. Further, there is a strong propensityof journals to publish weak controversial research tostimulate their citation index. The polarization of positionsis reflected in journals and their editorial stances. Meetingorganizers highlight controversial findings on dietarysalt, and feature low-quality research. The situation isnot much different from the efforts to reduce tobaccouse with mainstream public health and science on theone side and the tobacco industry and a few dissentingscientists on the other. It is notable that several dissentingscientists have acted as paid consultants of the Salt Institute- the most vocal opponent to public health actionson salt representing over 40 salt producers and food anddrink manufacturers over the past 40 years. At least oneof them is also indicated to have been a court witness forthe tobacco industry and was paid $450,000-$500,000USD to claim there was inadequate scientific proof thattobacco caused cancer. The World Hypertension Leaguehas called for quality research and for scientific meetingorganizers to have sessions on dietary salt that featurehigh-quality research, and the impact of financial conflictof interest and low-quality research on research findings.11Scientists and clinicians should view the dissidents andthe low-quality research they promote skeptically ratherthan creating situations that promote "false" equipoise.

Science is a quest for the truth and this can onlybe met by the conduct of rigorous carefully designedresearch. Much of the controversy generated aboutreducing dietary salt is based on commercial interestsand low-quality research very akin to the early days ofreducing tobacco use. The World Hypertension Leaguewith international partners oversee regularly updatedsystematic reviews of the literature on dietary salt toaid those interested in dietary salt to stay up to dateand to protect the implementation of one of the most cost-effective and beneficial public health interventionsacross the world.
 
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  1. Dietary Guidelines Advisory Committee. Scientific Reportof the 2015 Dietary Guidelines Advisory Committee. Part D.Chapter 6: Cross-cutting topics of public health importance.The Dietary Guidelines Advisory Committee, USA; 15 A.D.Feb 2.
  2. Campbell NR, Lackland DT, Niebylski ML. 2014 Dietary SaltFact Sheet of the World Hypertension League, InternationalSociety of Hypertension, Pan American Health OrganizationTechnical Advisory Group on Cardiovascular DiseasePrevention through Dietary Salt Reduction, the WorldHealth Organization Collaborating Centre on PopulationSalt Reduction, and World Action on Salt & Health. J ClinHypertens (Greenwich) 2015 Jan;17(1):7-9.
  3. Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA.Links between dietary salt intake, renal salt handling, bloodpressure, and cardiovascular diseases. Physiol Rev 2005Apr;85(2):679-715.
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  6. Adler AJ, Taylor F, Martin N, Gottlieb S, Taylor RS, Ebrahim S.Reduced dietary salt for the prevention of cardiovasculardisease. Cochrane Database Syst Rev 2014;12:CD009217.
  7. Aburto NJ, Ziolkovska A, Hooper L, Elliott P, Cappuccio FP,Meerpohl JJ. Effect of lower sodium intake on health:systematic review and meta-analyses. BMJ 2013;346:f1326.
  8. Campbell NR, Lackland DT, MacGregor GA. Dietary sodium:a perspective on recent sodium evidence - its interpretationand controversies. J Clin Hypertens (Greenwich) 2013Nov;15(11):765-768.
  9. Cobb LK, Anderson CA, Elliott P, Hu FB, Liu K, Neaton JD,Whelton PK, Woodward M, Appel LJ, American HeartAssociation Council on Lifestyle and Metabolic Health.Methodological issues in cohort studies that relate sodiumintake to cardiovascular disease outcomes: a science advisoryfrom the American Heart Association. Circulation 2014Mar;129(10):1173-1186.
  10. Campbell NR, Appel LJ, Cappuccio FP, Correa-Rotter R,Hankey GJ, Lackland DT, MacGregor G, Neal B, Niebylski ML,Webster J, et al. A call for quality research on salt intake andhealth: from the World Hypertension League and supportingorganizations. J Clin Hypertens 2014 Jul 16;16(7):469-471.
  11. Campbell NRC, Lackland DT, Lisheng L, Zhang X-H,Nilsson PM, Niebylski ML; World Hypertension LeagueExecutive. The World Hypertension League: where nowand where to in salt reduction. Cardiovasc Drugs Ther 2015Jun;5(3):238-242.
 
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