# The relationship between sodium intake and mortality: a case-cohort study in a population-based cohort of 148,000 adults with both 24-hour and spot urine samples

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $503,190

## Abstract

PROJECT SUMMARY
The largest cohort studies on the subject to date have found that adults with a low estimated sodium intake
had a higher risk of mortality than those with a sodium intake close to the population’s average. These findings
of a “J-shaped” sodium-mortality association have important implications for public health efforts on salt
because they suggest that reducing sodium intake at the population level could cause harm among a large
proportion of the population. Many investigators have criticized these cohort studies for their use of a spot
urine, rather than the gold-standard 24-hour urine sample, to estimate sodium intake. Thus far, however, the
debate on the shape of the sodium-mortality association could not be settled convincingly because analyses of
cohort studies that collected 24-hour urine samples have suffered from far smaller sample sizes than of those
that collected a spot urine. The overall objective of this project is to better understand the association of
sodium intake with mortality, particularly at levels of sodium intake below the population average in the US.
The central hypothesis is that the J-shape of the sodium-mortality association that has been reported by some
investigators is a result of bias from assessing sodium intake through use of a spot rather than a 24-hour urine
sample. This central hypothesis will be tested by pursuing three specific aims: 1) Determine the range of
sodium intake among adults that is associated with the lowest risk of all-cause mortality; 2) Determine whether
the commonly reported increased risk of mortality at low levels of sodium intake stems from using a spot urine
(rather than the gold-standard 24-hour urine) to estimate 24-hour sodium intake; and 3) Establish whether the
association of sodium intake with cardiovascular causes of death is the main determinant of the shape of the
sodium-mortality association. Using a case-cohort design, this project will analyze the sodium and potassium
concentration in urine samples collected as part of Lifelines, which is a population-based cohort study focused
on healthy aging in the Northern Netherlands. The Lifelines cohort has three unique features that enable the
investigators to make an important contribution to resolving the controversy about the J-shaped sodium-
mortality association: 1) Lifelines has collected two 24-hour urine samples from its participants; 2) with 147,888
adult participants and over 6,000 deaths (over a 15-year follow-up period), the Lifelines cohort has a far larger
sample size and number of deaths than any other cohorts that have collected 24-hour urine samples; and 3)
Lifelines has additionally collected a spot urine sample from all participants such that we are able to directly
compare the shape of the sodium-mortality association depending on whether a spot or the gold-standard 24-
hour urine sample is used. This project is significant because it will inform dietary guidelines on salt, and
whether public health e...

## Key facts

- **NIH application ID:** 10912432
- **Project number:** 5R01HL166509-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Pascal Geldsetzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $503,190
- **Award type:** 5
- **Project period:** 2023-08-23 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912432

## Citation

> US National Institutes of Health, RePORTER application 10912432, The relationship between sodium intake and mortality: a case-cohort study in a population-based cohort of 148,000 adults with both 24-hour and spot urine samples (5R01HL166509-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10912432. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*