An Annotated Bibliography

Science of Salt Reduction

Science of Salt Reduction

Overwyk KJ, Quader ZS, Maalouf J, et al. Dietary Sodium Intake and Health Indicators: A Systematic Review of Published Literature between January 2015 and December 2019. Adv Nutr. 2020;11(5):1174-1200.

This systematic review evaluates recent literature on the association between salt intake and health outcomes. Most studies published since 2015 do not address the research gaps or meet the recommendations for research methods outlined in the 2013 Institute of Medicine report on the scientific evidence on sodium and health outcomes. Reasons for this could include a lack of knowledge about the recommendations, resources necessary, or time for implementation and reporting. Most of the published evidence on sodium and CVD risk between 2015 and 2019 was observational (a high number were cross-sectional) rather than interventional, thus subject to potential bias from error in assessment of sodium intake and confounding. Observational studies with clinical end points (CVD, mortality, etc.) had mixed results (positive, null, and negative). Further research is required, particularly RCTs examining the effects of sodium on CVD outcomes among the general population and for specific populations that are at higher risk, including chronic heart failure patients.



Dietary Guidance on Sodium and Potassium Intake

Guideline: Sodium Intake for Adults and Children. Geneva: World Health Organization; 2012.

WHO recommends that adults consume less than 2,000 mg of sodium, or 5 grams of salt per day. WHO also recommends a reduction in sodium intake to control blood pressure in children. For children, the recommended maximum for adults should be adjusted downward based on energy requirements of children relative to those in adults. A diet high in sodium increases the risk of raised blood pressure and increases the risk of heart disease and stroke. Reducing sodium intake significantly reduces blood pressure in both children and adults and has no adverse effects on blood lipids or renal function.

Guideline: Potassium Intake for Adults and Children. Geneva: World Health Organization; 2012

WHO recommends that adults consume at least 3150 mg of potassium per day to reduce systolic and diabolic blood pressure and risk of cardiovascular disease in adults. An increase in potassium intake from food is also suggested for control of blood pressure in children. Evidence suggests that higher potassium intake has no adverse effect on blood lipids or renal function in adults but can decrease risk of cardiovascular disease, have beneficial effects on bone mineral density, and mitigate the negative effect of high sodium consumption. An uptake in potassium consumption can be achieved through the increased consumption of food high in potassium such as fresh fruit, vegetables, and beans.



Effect of Sodium on Blood Pressure

Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3-10.

The DASH sodium study randomized participants to be fed three different sodium levels (3,400, 2,300 and 1,150 mg/day) of either the DASH diet (diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, poultry, fish, and nuts) or a typical diet for 30 days at each sodium level. Among participants on the typical diet, those randomized to intermediate and low sodium levels saw a significant reduction in systolic BP of 2.1 mmHg and 6.7mmHg, respectively. Participants randomized to the DASH diet had even greater decreases in blood pressure at the low sodium levels. Compared to the typical diet group with high intake, they achieved systolic BP decreases of 7.1mm Hg (without hypertension) and 11.5 mm Hg (with hypertension). Both diets showed a progressive effect, with greater decreases in BP with further reductions in sodium intake.

Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group. BMJ. 1988;297(6644):319-328.

Across 52 locations in 32 countries, median urinary sodium excretion values ranged from 4.6 mg/24 h to 5,568.3 mg/24 h. In the four study sites with very low sodium excretion, blood pressure was also found to be low, and there was no significant age-related rise in blood pressure. There was a linear relationship between the median 24-hour urinary sodium excretion and the slope of systolic and diastolic BP with age. After adjustment for body mass index and alcohol intake, all sites demonstrated this same relationship.

He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ. 2013;346:f1325.

“A 100 mmol reduction in 24-hour urinary sodium (~6 g/day salt) was associated with a fall in systolic blood pressure of 5.8 mm Hg (2.5 to 9.2, P=0.001) after adjustment for age, ethnic group, and blood pressure status”. Additionally, data from the two trials that compare multiple salt intake levels over time suggest a dose-response relationship with salt intake and BP, with larger salt reductions resulting in greater BP decreases. Reducing salt intake from the average of the analyzed trials (9.4 g/day) to 5-6 g/day would have significant impacts on lowering blood pressure, but reductions to 3 g/day would provide even greater benefits.

For similar article, see:
Filippini T, Malavolti M, Whelton PK, et al. Blood Pressure Effects of Sodium Reduction: Dose-Response Meta-Analysis of Experimental Studies. Circulation. 2021. 143,16: 1542-1567.

Geleijnse JM, Hofman A, Witteman JC, et al. Long-term effects of neonatal sodium restriction on blood pressure [published correction appears in Hypertension 1997 May;29(5):1211]. Hypertension. 1997;29(4):913-917.

Using participants from a 1980 Dutch study that showed that “sodium intake was positive related to BP during the first 6 months of life”, this current study demonstrated that sodium intake during infancy may be associated with blood pressure later in life. Fifteen years after the 1980 study, 35% (167) of the original participants were selected for follow up. Compared to the control group (normal sodium intake), the low sodium intake group had 3.6 mm Hg lower systolic blood pressure (−6.6 to −0.5, p=.02) after controlling for confounding factors. Significant differences were not reported between groups for urinary sodium excretion.



Effect of Sodium on Health Outcomes

Added November 2022: Ma Y, He FJ, Sun Q, et al. 24-Hour Urinary Sodium and Potassium Excretion and Cardiovascular Risk. NEJM. 2022. 386,3: 252-263.

A pooled analysis of 6 major prospective cohort studies which collected multiple gold standard 24-hour urine samples found a significant linear, dose-response association between sodium intake and cardiovascular risk between 2,000 mg and 6,000 mg sodium/day. The study included 10,000 generally healthy adults followed for an average of 8.8 years. Higher potassium intake and a lower sodium-to-potassium ratio were also associated with significantly lower levels of cardiovascular disease. For every 1,000 mg per day increase in sodium excretion, a person’s risk for cardiovascular disease rose by 18%; a 1,000 increase in potassium excretion decreased cardiovascular risk by 18%. Sodium intake was also positively associated with cardiovascular mortality (but not all cause mortality). Both higher potassium excretion and a lower sodium-to-potassium ratio were associated with a lower risk of all-cause mortality, including cardiovascular risk. Though many cohort studies have found J or U-shaped relationships between sodium intake and cardiovascular risk, these have primarily relied upon spot urine collection and occasionally a single 24-hour urine collection. This is the first meta-analysis to include only the gold standard of multiple 24-hour urine collections.

For similar articles, see:
Wang YJ, Yeh TL, Shih MC, et al. Dietary Sodium Intake and Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-Analysis. 2020. Nutrients. 12,10 2934.

Aburto NJ, Ziolkovska A, Hooper L, et al. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ. 2013;346:f1326.

Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 2007;334(7599):885-888.

One of the few trials assessing the impact of sodium intake on CVD, this study used long-term follow-up data from 3,126 prehypertensive adult participants of the trials of hypertension prevention (TOHP) to determine effects on cardiovascular disease outcomes. Participants were randomized to a control group or a sodium reduction intervention group lasting 18 months (TOHP I) or 36-48 months (TOHP II). The intervention groups showed a 30% reduction in cardiovascular disease and a 20% reduction in mortality compared to the control groups.



Sodium and Potassium

Perez V, Chang ET. Sodium-to-potassium ratio and blood pressure, hypertension, and related factors. Advances in Nutrition. Advances in Nutrition. 2014 Nov 3;5(6):712-41.

Both reduced sodium intake and increased potassium intake have been reported to reduce blood pressure. This systematic review concluded that “the sodium-to-potassium ratio (Na-K ratio) is more strongly associated with blood pressure outcomes than either sodium or potassium alone in hypertensive populations”.



Modeling Impact and Cost-effectiveness of Sodium Reduction

World Health Organization. Saving lives, spending less: a strategic response to noncommunicable diseases. World Health Organization; 2018.

Reducing unhealthy diets through reducing salt intake is considered a “Best Buy intervention” by the WHO. Recommended interventions to reduce salt intake include reformulation of food products, establishing a supportive environment in public institutions by providing low-salt options, education through behavior change communication and mass-media campaigns, and front-of-pack labelling. Investment in salt reduction activities offers the highest return among all Best Buy interventions, an estimated US$12.82 return on every US$1 invested.

Kontis V, Mathers CD, Rehm J, et al. Contribution of six risk factors to achieving the 25× 25 non-communicable disease mortality reduction target: a modelling study. The Lancet. 2014 Aug 2;384(9941):427-37.

Following the 2013 World Health Assembly, global commitments were made to reach a 25% relative reduction in premature mortality from non-communicable diseases (NCDs) by 2025. This study estimates that achieving the targets for six risk factors, including a 30% reduction in salt intake (others include tobacco and alcohol use, obesity, and raised blood pressure and glucose), would result in a decreased probability (-22% in men, -19% in women) of dying from any of the four major NCDs (cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes).

Webb M, Fahimi S, Singh GM, et al. Cost effectiveness of a government supported policy strategy to decrease sodium intake: global analysis across 183 nations. BMJ. 2017 Jan 10;356:i6699.

In a global modeling study across 183 countries, the cost effectiveness of a 10-year government “soft regulation” policy consisting of combined targeted industry agreements and public education to reduce population sodium consumption by 10% was approximately I$204 per DALY saved with a population weighted mean cost of I$1.13 per capita. Nearly 5.8 million DALYs/year related to CVD would be averted. Cost effectiveness estimates widely ranged by country; however, in all but one country the interventions were cost effective as per the WHO benchmark (<3×GDP per capita).



Assessing Taste and Acceptability of a Reduced Sodium Diet

Bobowski N. Shifting human salty taste preference: potential opportunities and challenges in reducing dietary salt intake of Americans. Chemosensory Perception. 2015 Sep 1;8(3):112-6.

Dietary salt preference largely stems from one’s individual salt intake habits. Those who consume high sodium levels prefer the taste of high salt. This review paper highlights findings such as the impact of early exposure to salty foods in determining salt preference later in life, the ability for salt preference to change over time after limiting exposure, and the tendency not to overcompensate for low-sodium foods by adding salt at the table. Gaps in the research are also discussed, such as whether children’s salt preference can be shifted and why humans desire and consume salt in the absence of biological need.

Beauchamp GK, Bertino M, Engelman K. Failure to compensate decreased dietary sodium with increased table salt usage. JAMA. 1987;258(22):3275-8.

When sodium was reduced by nearly 50% in foods served to study participants, participants only added 20% back with a salt shaker at the table. Throughout the study, participants did not report any changes in taste perception.

Jaenke R, Barzi F, McMahon E, et al. Consumer acceptance of reformulated food products: A systematic review and meta-analysis of salt-reduced foods. Critical Reviews in Food Science and Nutrition. 2017 Nov 2;57(16):3357-72.

“[S]alt can be reduced in breads and processed meats by up to 37% and 67%, respectively, without a decrease in consumer acceptability.” For cheese products, meta-analysis showed decreasing levels of acceptance with reduced amounts of salt. Acceptance was lower in studies with salt reduction above 60%. Results varied for other products. Acceptability of products using low-sodium salts or flavor compensation were also studied. Replacing up to 50% of salt with potassium chloride in meat products or up to 30% in cheese was not found to impact acceptability.



Sodium and Iodine

Because many populations primarily consume iodine through salt fortification, there is concern that reduction of salt intake will lead to inadequate consumption of iodine. Iodine fortification has been a major and successful public health initiative over the past 2-3 decades. Thus, it is important that progress in this area is not hindered but complemented by salt reduction strategies.

Added November 2022: World Health Organization. Universal salt iodization and sodium intake reduction: compatible, cost-effective strategies of great public health benefit. Published 22 August 2022.

Programs and policies for salt iodization and salt reduction can and should go hand in hand as a strategy to reduce the burden of hypertension and cardiovascular disease. Both require food industry and service operator engagement and similar surveillance modalities, making it possible to jointly implement both initiatives. Suggested key activities include coordinating policy development and implementation through regulatory policies, such as adjusting the iodine concentration in salt given a population sodium intake and regulating sodium levels in processed foods. Coordinated monitoring and surveillance of iodine and sodium intake through joint surveys and evaluations is recommended, managed by cross disciplinary research programs. Communication and advocacy efforts should also be conducted jointly, as well as investment, to maximize the effectiveness and reach of both programs.

Verkaik-Kloosterman J, van Veer P, Ocké MC. Reduction of salt: will iodine intake remain adequate in The Netherlands?. British Journal of Nutrition. 2010 Dec;104(11):1712-8.

This modeling study in a Dutch population found that salt reductions of 12, 25 or 50% in industrially processed foods decreased mean salt intake by 7, 15 and 30% compared with current intake, and mean iodine intake by 6, 12 or 25%. Iodine intake levels remained adequate at all salt reduction levels for most the population. Reducing both discretionary salt and salt in industrial foods by 50%, led to a slight increase (1-11%) in inadequate iodine intakes for age groups above 3 years. For children aged 1-3 years, all scenarios led to inadequate iodine levels, affecting between 10% (12% industrial reduction) to 35% of the population (50% reduction industrial + discretionary). However, if industry meets the target of using iodized salt in 50% of industrially processed foods, there would be “adequate iodine intakes for virtually the whole population, including young children” for all scenarios.

Charlton K, Ware LJ, Baumgartner J, et al. How will South Africa’s mandatory salt reduction policy affect its salt iodisation programme? A cross-sectional analysis from the WHO-SAGE Wave 2 Salt & Tobacco study. BMJ Open. 2018;8(3):e020404.

In this cohort study of older South Africans, salt intake (measured by 24-hour urine) was positively associated with 24-hour iodine excretion (p<0.001). Those in the lowest salt intake category (<5g/day) did not meet iodine requirements (95 μg/day). Salt reduction programs may need to be accompanied by further iodine fortification efforts, and intake of both nutrients should be monitored simultaneously.

He FJ, Ma Y, Feng X, et al. Effect of salt reduction on iodine status assessed by 24 hour urinary iodine excretion in children and their families in northern China: a substudy of a cluster randomised controlled trial. BMJ Open. 2016;6(9):e011168.

In an RCT, a ~3.5-month school-based educational salt reduction program in northern China led to a significant decrease in salt intake of 1.9 g/day in children and 2.9 g/day in adults. Although iodine intake also decreased (19.3% in children and 11.4% in adults), iodine intake remained adequate.

For similar articles, see:
Campbell NR, Dary O, Cappuccio FP, Neufeld LM, Harding KB, Zimmermann MB. Need for coordinated programs to improve global health by optimizing salt and iodine intake. Rev Panam Salud Publica. 2012;32(4):281-286

Science of Salt Reduction