Sodium and Health: Evidence, Policy, Reality

Sodium and Health: Evidence, Policy, Reality Cheryl A. M. Anderson, PhD, MPH, MS University of California San Diego Department of Family Medicine and Public Health Email: c1anderson@ucsd.edu

Sodium Intake in Populations: Assessment of Evidence Statement of Task The CDC asked the IOM to examine the studies on sodium intake and direct health outcomes in the general U.S. population and among individuals with hypertension; pre-hypertension; those 51 years of age and older; African Americans; and those with diabetes, chronic kidney disease, and congestive heart failure. Source: Institute of Medicine Consensus Report, Released May 14, 2013

Outline Evidence related to sodium and health outcomes Sodium: an old enemy or a new friend? Recent policy making on sodium Individual and public health PopulaAon sodium reducaon RealisAc? Feasible? Sustainable?

Points to consider! Sodium has been evaluated in relation to cardiovascular, kidney, and cancer outcomes! Policies mostly based on evidence that reduced sodium intake lowers blood pressure! Lower levels of blood pressure should reduce the risk of cardiovascular disease, the leading cause of death in the US and worldwide! The estimated benefits of sodium reduction are substantial and warrant major public health efforts to reduce intake

Survey approaches to Sodium Assessment: Approach Characteristics Behavioral Strumylaite et al, Medicina 2006 Qualitative food pattern Sjodahl et al, Cancer Epi Biomarkers Prev 2008 Semi-quantitative usual intake Peleteiro et al, Br J Cancer 2011 Do you put additional salt on your meal? Categorized as yes or no How often do you sprinkle extra salt on your hot food? How often do you eat salted meat? Categorized as high or low based on frequency data Food list, frequency and amount used to determine intake Categorized as high or low

Food Frequency QuesAonnaire Derives typical intake from quesaons on amount and frequency PotenAal for misreporang Incomplete list of foods and aggregaaon Poor poraon size esamaaon PotenAal for recall bias PotenAal for underesamaaon DiscreAonary sodium intake not assessed

24-hour recall interview Requires detailed probing Databases must have specific sodium content of processed foods that contribute most to daily intake Multiple recalls needed to account for dayto-day variability 9

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Optimal Measurement of Na Intake Multiple, high quality 24 hour urine collections Suboptimal 24 hour urine collected with limited or no attention to quality control Spot, overnight or timed urines 24 hour dietary recalls Food frequency questionnaire

Adverse Effects of Excess Sodium Intake! Established relationship! Increased blood pressure! Probable relationship! Gastric cancer! Suggestive relationship! Increased risk of osteoporosis! Increased left ventricular mass! Hypothesized relationship! Overweight/obesity! CVD and Stroke

Types of Evidence Linking Sodium Intake to Blood Pressure Epidemiology Migration Genetic Animal Trials Population Interventions Over 50 population studies Several, e.g. Kenya All defects identified so far impair the ability of the kidney to excrete salt. All forms of hypertension are caused or aggravated by salt No study has documented increased CVD risk from reduced sodium Children: ~10 trials, one trial in infants Adults: > 50 trials, 10 dose-response Northern Japan Finland Portuguese villages

Does modification of whole dietary patterns affect blood pressure? Dietary Approaches to Stop Hypertension (DASH) Trial DASH diet emphasizes: Fruits Vegetables Low-fat dairy products Whole grains Poultry Fish Nuts Reduced red meat Reduced sweets and sugared-beverages

D.A.S.H. Diets and Systolic BP Change 132 Systolic BP (mmhg) 130 128 126 124 122 0 1 2 3 4 5 6 7&8 Control Fruits/Vegs Combination Intervention Week Source: Appel LJ et al. N Eng J Med 1997;336:1117-1124

Study Design Randomization Control Diet N = 412 Higher Sodium Intermediate Sodium Control Diet, N = 204 DASH Diet, N = 208 Higher Sodium Intermediate Sodium Lower Sodium Lower Sodium Run-in: (11-14 days) Intervention (Three 30-day periods, random order)

D.A.S.H.-SODIUM Diets and Systolic BP Change Source: Sacks FM et al, N Engl J Med. 2001 Jan 4;344(1):3-10

Estimated BP Reductions from Lowering Sodium Intake SBP (mmhg) DBP (mmhg) Na (mg/d) Reduction Children 1 Non-HTN 2 HTN 2 HTN 3 Resistant -1.2-2.0-5.0-22.7-1.3-1.0-2.7-9.1 n/a 1,700 1,800 2,300 1 He,HTN 2006;48:861 2 Cochrane Review, 2006; 3 Pimenta, HTN 2009;54:475

Trials of Sodium Reduction in Patients with Diabetes 13 trials with 254 individuals 75 individuals with type 1 diabetes 158 individuals with type 2 diabetes Duration median: 1 week, range: 5 days to 12 wks *Source: Suckling RJ, Cochrane Review, 2010 Dec 8;(12):CD006763

BP Reductions from Lowering Sodium Intake: Diabetes Type 1 DM Type 2 DM SBP (mmhg) -7.1-6.9 DBP (mmhg) -3.1-2.9 Median Na (mg/d) Reduction 4,700 2,900 *Source: Suckling RJ, Cochrane Review, 2010 Dec 8;(12):CD006763

Population-Based Strategy SBP Distributions After Intervention Before Intervention Reduction in BP Stamler R. Hypertension 1991;17:I-16 I-20. Reduction in SBP mmhg 2 3 5 % Reduction in Mortality Stroke CHD Total -6-4 -3-8 -5-4 -14-9 -7

Projected Effects of Dietary Salt Reduction Source: Bibbins-Domingo, K et al, N. Engl. J Med; 2010; 362:590-599

Sodium Reduction Lowers CVD Risk: Meta-Analysis of Trials Events Na/Cntl Trial TOHP I 17 / 32 TOHP II 71 / 80 Morgan 6 / 5 TONE 36 / 46 Total 130 / 163 Source: He FJ, MacGregor GA. Lancet. 2011;378:380 382

Trials of Sodium Reduction in Heart Failure Multiple, randomized controlled studies by one investigative team (Paterna et al, 2009, 2011) Low sodium intake (to 1840 mg/day) increases risk for adverse events

Trials of Sodium Reduction in Heart Failure Participants Hospitalized NYHA Class III Heart Failure Intensive medication regimens 100% ACEI 100% Lasix 85% Spironolactone Medical management Unconventional, leading to untreated long-term volume depletion Source: Paterna, Am J Card 2009:103:93, Paterna, Am J Med Science 2011, 342: 27

Methodological Challenges in Observational Studies that Relate Sodium Intake to CVD Random error in sodium assessment Systematic error in sodium assessment Potential for reverse causality Major analytic issue, e.g. under-adjustment Potential for residual confounding 26 studies with 31 independent samples On average, 2.5 issues/study Source: Cobb LC et al, 2012 Circulation

Random and Systematic Error in Measuring Na Intake Random error Reason: high day-to-day variability of Na within an individual Impact: bias to the null Systematic error Reason: underreporting of intake from 24 hr recalls OR incomplete urine collection Impact: potential for paradoxical relationship Both types of errors extremely common

Increased CVD Mortality in Persons with Lowest Na (by quartile of Na Intake in mg/d) Hazard Ratio (HR) 3 2 1 1.8 1.94 1.48 P=0.03 Q1 vs Q4 1 0 1st 2nd 3rd 4th Na Quartile of based on mg of Na/d Source: Cohen, JGIM 2008;23:1297-302

Case of Systematic Error Leading to Bias: Increased CVD Mortality in Persons with Lowest Na (by quartile of Na Intake in mg/d) Hazard Ratio (HR) 3 2 1 1.8 1.94 1.48 P=0.03 Q1 vs Q4 1 0 1st 2nd 3rd 4th Na Quartile of based on mg of Na/d Source: Cohen, JGIM 2008;23:1297-302

Evidence of Contamination Evidence in a Cohort of Massive Study 1 (NHANESIII) Reporting Underreporting Increased Mortality of Calorie in Persons Intake with Low Sodium Intake Leading on 24Hr to Systematic Dietary Recall Error in Estimate or Sodium Intake Quartile of Sodium Intake: 1 st (Lowest) 2nd 3rd 4 th (Highest) Na (mg/d) 1,501 2,483 3,441 5,497 Energy Intake (kcal) 1,282 1,762 2,152 2,938 BMI (kg/m 2 ) 25.8 26.4 26.3 26.6 1 Cohen, JGIM 2008;23:1297-302

Reduced Systematic Error from Use of Na/Kcal Ratio as Exposure instead of Na/d 2 Hazard Ratio (HR) 1 1.25 0.9 0.9 P=0.26 Q1 vs Q4 1 0 1 Cohen, JGIM 2008;23:1297-302 1st 2nd 3rd 4th Na Quartile of based on mg of Na /Kcal

J-Shaped Relationship of Total Mortality with Urine Sodium Excretion in Patients with Type 1 Diabetes Extremely low levels are most likely the result of extreme undercollection Thomas, Diabetes Care 2011: 861-6

Example of Low Sodium Excretion Related to Under-collection 78 year old women, screened for a trial No special diet 172 pounds (81 kg), 5 2, BMI 31 kg/m 2 Two 24 hour urine collections required Detailed instructions provided Urine Lab Range Expected 1st 2nd Sodium (mmol/24hr) 100? 18 21 Volume (ml/24hr) >500 800 725 Creatinine (g/24 hr).63 to 2.5 1.2.41.09

Evidence Summary Adverse effects of excess sodium intake Established adverse effect on blood pressure, CVD, and stroke Probable or suggestive relationship for gastric cancer, osteoporosis, and left ventricular mass Adverse effects of low sodium intake Suggestive relationship of increased mortality in those with heart failure or diabetes

Upper Limit of Sodium Intake Set at 2300 mg/day It is not a recommended intake Stated that consuming an intake above the lower limit for sodium provides no benefit Source: IOM Dietary Reference Intakes for Electrolytes and Water

Adequate Intake for Sodium Set at 1500 mg/day Nutrient Adequacy - a diet that provides 1500 mg/day can also provide an adequate intake of other important nutrients (e.g., DASH Diet) Sufficient to cover sodium sweat losses when exposed to high temperatures or in moderate physical activity Source: IOM Dietary Reference Intakes for Electrolytes and Water

2010 Dietary Guidelines for Americans recommendeds a gradual reduction in the amount of sodium in the diets of Americans to 2,300 milligrams per person daily, and 1,500 milligrams for some special populations.

2013 AHA/ACC Lifestyle Report For blood pressure lowering: lower sodium intake, in general; or consume no more than 2,400 mg of sodium/ day For even greater reduction in blood pressure: lower sodium intake to 1,500 mg per day; or Lower sodium intake by at least 1,000 mg per day even if goals of 2,400 or 1,500 mg per day cannot be met.

Policy Summary Policies in place (national and international) NYC DOH efforts have lead to voluntary initiatives by food manufacturers and restaurants Progress hindered by: Confusion resulting from confusing terminology ( saltsensitive, salt-resistant hypertension) Activities of pro-sodium lobby groups Prominent scientists with opposite opinions

Sources of Dietary Sodium Food Processing 77% Inherent 12% At the Table 6% During Cooking 5% Source: Mattes and Donnelly, 1991, J Am Coll of Nutr, 10(4): 383-93

*Includes breads, cereals, grains, processed meats and dairy, soups, gravies, sauces Source: Anderson C et al, J Am Diet Assoc, 2010;110:736-745

Source: Johnson CM et al. Arch Intern Med. 2010;170 732-734

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Industry Sodium Reduction Initiatives 2010 Company Kraft ConAgra PepsiCo Campbell s Soup Plans to reduce sodium By 10% over next 2 years, in select products By 20% over next 5 years, in all products By 25% over next 5 years, in all products By 35% over next 4 years; in past 4 years reduced100 products by 25-50%

Reality Summary! Current levels of sodium intake exceed physiologic need and guidelines! Over 75% of sodium comes from packaged, processed, and restaurant foods! There are outspoken critics of population-based recommendations to reduce sodium intake! Need rigorous investigations of consequences of low sodium intake

Balancing evidence, policy, and reality! New evidence suggestive of adverse effects from low sodium intake must be considered in new policy making for general population and especially population subgroups! The estimated benefits of sodium reduction are substantial and warrant major public health efforts to reduce intake