Targeting the dietary Na:K ratio – considerations for design of an intervention study to impact blood pressure

Authors: Baer, David; ALTHOUSE, ANDREW - University Of Pittsburgh; HERMANN, MINDY - Consultant; JOHNSON, JANICE - Cargill Corporation; MAKI, KEVIN - Midwest Biomedical Research; MARKLUND, MATT - Tufts University; VOGT, LIFFERT - University Of Amsterdam; WESSON, DONALD - Texas A&M University; STALLINGS, VIRGINA - Children'S Hospital - Philadelphia, Pennsylvania

Submitted to: Advances in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/6/2021
Publication Date: 9/1/2021
Citation: Baer, D.J., Althouse, A., Hermann, M., Johnson, J., Maki, K.C., Marklund, M., Vogt, L., Wesson, D., Stallings, V.A. 2021. Targeting the dietary Na:K ratio – considerations for design of an intervention study to impact blood pressure. Advances in Nutrition. 13(1):225-233. https://doi.org/10.1093/advances/nmab099.
DOI: https://doi.org/10.1093/advances/nmab099

Interpretive Summary: Understanding of the relationship between the ratio of sodium and potassium (Na:K) and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium and other government reports. Despite these recommendations, over the past several decades, little progress has been made toward reducing sodium intake, and the potassium intake of Americans consistently is below the level that is recommended. Hypertension persists as among the most prevalent non-communicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including COVID-19. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. A large body of evidence links high dietary sodium intake to elevated blood pressure and increased risk of cardiovascular and kidney disease. In tandem with sodium, dietary potassium plays a well-established role in blood pressure regulation. Over the past several decades, little progress has been made toward reducing sodium intake, and the potassium intake of Americans consistently is below the level that is recommended. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. A research study to elucidate the role of the Na:K ratio in blood pressure management must address several considerations: the target study population characteristics and size; study design; the range of dietary Na:K ratios to study in a controlled fashion; protocols for blood pressure measurement; and desired end points, namely preventing normotensive individuals from developing elevated blood pressure (formerly called pre-hypertension), preventing individuals with elevated blood pressure from transitioning into hypertension, and/or lowering blood pressure in individuals with stage 1 or stage 2 hypertension. This paper addresses these decisions points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and could help inform the next iteration of Dietary Reference Intakes for sodium and potassium.

Technical Abstract: Despite medical, dietary, and lifestyle recommendations and drug advancements, hypertension persists as among the most prevalent noncommunicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including cardiovascular and renal responses. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. In fact, the understanding of the relation between this ratio and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. The successful translatability of such a trial will require careful consideration of study elements, including the study population, duration, blood pressure measurement, and dietary intervention, among other factors. This paper addresses these decision points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and would inform the next iteration of Dietary Reference Intakes for sodium and potassium.