Which recovery biomarker is the gold standard for estimating Na and K intake?

From the Neuhouser Group, Public Health Sciences Division

On average, Americans consume about 3,400 mg of sodium (Na) per day.  The Dietary Guidelines for Americans recommend limiting sodium intake to less than 2,300 mg of sodium per day – that’s about one teaspoon of table salt.   A majority of people, globally and nationally, consume less than the recommended amount of potassium (K). An adult should consume about 3,500-4,700 mg daily.   Globally and nationally, dietary guidance is provided to individuals; therefore, it’s important to have accurate intake assessments of these minerals. Although one of the most popular ways to assess the intake of sodium and potassium is via self-reporting, this method is often unreliable due to recall bias and response error. However, 24-hour urinary measures, considered the gold standard recovery biomarkers and intake assessments for sodium and potassium, provide a quantitative estimate of intake that can improve upon self-reporting.  However, collecting 24-hour urine samples can be burdensome and expensive for epidemiologic studies.  We need a better way.  Single spot urine collections are an attractive alternative and have been investigated, yet, due to variations of metabolite excretion through the day and night, the success of a single spot urine has been elusive.  Dr. Tinker, from the Division of Public Health Sciences and the first author of the study explained, “Science has yet to tame single spot urine collections for estimating 24-hour urine collection excretions of important nutrients.  And, even a 24-hour urine collection, the gold standard, isn’t so straight forward.” Economic and participant burden can drastically decrease the use of 24-hour urine collection in population-based studies. 

There are two quantitative methods for collecting concentrations of Na and K – 24-hour urine collection and spot urine collection. For this study, the first void of the morning was collected into a provided, special container, followed by participants collecting urine for the next 24 hours.  Spot urines may collected and tested at any time, and for some studies, individual spot urines are collected in individual containers for the 24-hour period, thus can be used to assay a spot urine sample, then mixed to assay the 24-hour collection.   In this particular study, participants collected up to 120 mL of the first urine of the day as the spot urine and discarded the remainder.  The entire spot urine may also be collected as a method.  To test a spot urine against a 24-hour collection, assessing both is needed, as is an accurate assessment of Na and K intake, such as a controlled feeding study, which this study protocol utilized.  There are few studies on the comparisons of Na and K utilizing these 2 methods in a controlled-feeding design, often due to expense. Therefore, Drs. Neuhouser and Lampe, conducted a study to evaluate a measured 24-hour urine collection and 4 algorithms for estimating 24-hour excretion of Na and K from a first void urine sample and to develop enhanced algorithms by adding participant characteristics to the measured and estimated 24-hour urine excretions of Na and K.  The Neuhouser Group utilized four algorithms in this study: The Kawasaki, Tanaka, Mann, and INTERSALT algorithms, from well documented and published studies.  Dr. Tinker elaborated on the complexity of the study, “As much as we’d like simple answers to assessing dietary intake through objective biologic measurements, each nutrient, each biospecimen, and each laboratory method affect the search.” Their paper explains the similarities and differences of the algorithms and is published in Current Developments in Nutrition.

 The Women’s Health Study (WHI) recruited postmenopausal women; these participants were enrolled in 1 or more of 4 clinical trials as part of the Women’s Health Study. This subsample of participants (n=153) for this study were enrolled in a 2-week controlled feeding study at Fred Hutchinson Cancer Research Center for the WHI Seattle Clinical Center. This study is one of several under the Nutrition and Physical Activity Assessment suite of studies in the WHI that commenced in 2004 and is ongoing, initially through WHI funding and subsequently through a series of successful new and competing renewal grants.  The participants in this study were provided food for two weeks from the Prevention Center’s Human Nutrition Lab based on their usual intake as 4-day rotating menus and foods that were individually developed based on their usual consumption of foods and beverages.  Participants returned the uneaten foods, which were documented in detail and subtracted from the provided foods data to compute a consumed intake, including the provision and measurement of salt from provided saltshakers.  Body weight was measured. For energy expenditure, the participants completed a doubly labeled water biomarker assessment on the first and last day of the 2-week study period. They were also given a kit and instructions for collection of the first-void spot urine and the 24-hour urine for Na and K assessments. The Neuhouser group used various statistical methods (algorithms and Pearson’s correlation) to determine the 24-hour urine collections for Na and K intake.


Graphical Representation of Figure 1. Measured and estimated 24-hour urine sodium and potassium from spot urine (n=150)
Figure 1. Measured and estimated 24-hour urine sodium and potassium from spot urine (n=150) Image from Dr. Tinker Click for high-resolution image

Na and K urine excretions from the 24-hour urine collection had significantly higher correlations with the consumed and quantified intakes of Na, K, and both; these correlations were higher than any of the estimated 24-hour urine values derived from a spot urine sample. Also, there were similarities for the correlations between the measured 24-hour electrolytes and the estimated 24-hour electrolyte values.  This study reports that spot urine algorithms are inefficient substitutes for a measured 24-hour urine assessment of Na and K intake.  It’s important to understand that participant burden can influence how 24-hour urine is collected in large studies. The Neuhouser group recommends utilizing the 24-hour urine collection, because it is thus far, the gold standard for estimating Na and K intake.  But, the search must go on for a less burdensome and more cost efficient method.

This study’s design is unique and rare due to the individualized menus; more controlled feeding studies are needed to accurately assess mineral and other nutrient intake.  Dr. Tinker elaborates on the developments of the study, “We continue to learn about urinary excretion, both 24-hour and spot, regarding elements to consider when using urine excretion as a biomarker of dietary intake.  This learning is often formed, as in this work, through the lens of limitations.  Limitations, though not the goals, can be useful in forwarding scientific progress.”  Future directions may include additional details relevant to Na and K excretion, such as environmental conditions, health and social determinants of health, and collaborative study initiatives that support combining data from feeding studies with diverse participant characteristics.  Dr. Tinker concluded, “Finding a cost-efficient, effective and reliable means in epidemiologic research to assess sodium and potassium intake can greatly assist public health science efforts in diet-disease and diet-health relationships.” 

This research was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Service.

Fred Hutch/UW Cancer Consortium members Ross Prentice, Johanna Lampe, and Marian Neuhouser contributed to this work.

Tinker LF, Huang Y, Johnson KC, Carbone LD, Snetselaar L, Van Horn L, Manson JE, Liu S, Mossavar-Rahmani Y, Prentice RL, Lampe JW. Estimating 24-Hour Urinary Excretion of Sodium and Potassium Is More Reliable from 24-Hour Urine Than Spot Urine Sample in a Feeding Study of US Older Postmenopausal Women. Current developments in nutrition. 2021 Nov;5(11):nzab125.  https://doi.org/10.1093/cdn/nzab125