Low Sodium Intake, Low Protein Intake, and Excess Mortality in an Older Dutch General Population Cohort: Findings in the Prospective Lifelines-MINUTHE Study

Background: Several studies have found a U-shaped association between sodium intake and mortality. The increased mortality risk of low sodium intake has raised debates and hampers widespread acceptance of public health campaigns and dietary guidelines on reducing sodium intake. Whether the excess risk can be attributed to low sodium intake alone or concomitant inadequate intake of other relevant nutrients is unknown. Objective: We investigated whether concomitant low protein intake could explain the lower part of the U-shaped association of sodium intake with all-cause mortality. Methods: We included 1603 individuals aged between 60 and 75 years old from the gender- and socioeconomic status-balanced prospective Lifelines-MINUTHE cohort study. Using multivariable Cox regression analyses, we investigated the association of sodium intake (24 h urinary sodium excretion) with all-cause mortality, including the interaction with protein intake calculated from the Maroni formula. Results: Mean intakes of sodium and protein were 3.9 &plusmn: 1.6 g/day and 1.1 &plusmn: 0.3 g/kg/day, respectively. After a median follow-up of 8.9 years, 125 individuals (7.8%) had died. The proportion of participants with insufficient protein intake (&lt:0.8 g/kg/day) was inversely related to sodium intake (i.e., 23.3% in Q1 versus 2.8% in Q4, p &lt: 0.001). We found an increased risk for mortality in both the highest quartile (Q4, &gt:4.7 g/day: hazard ratio (HR) 1.74 (95% confidence interval (CI) 1.03&ndash:2.95)) and the lowest two quartiles of sodium intake (Q1, 0.7&ndash:2.8 g/day: 2.05 (1.16&ndash:3.62): p = 0.01 and Q2, 2.8&ndash:3.6 g/day: 1.85 (1.08&ndash:3.20): p = 0.03), compared with the third quartile of sodium intake (Q3, 3.6&ndash:4.7 g/day). This U-shaped association was significantly modified by protein intake (Pinteraction = 0.006), with the increased mortality risk of low sodium intake being reversed to the lowest mortality risk with concomitant high protein intake. In contrast, the increased mortality risk of low sodium intake was magnified by concomitant low protein intake. Conclusions: We found that a higher protein intake counteracts the increased mortality risk observed in subjects with a low sodium intake. In contrast, a joint low intake of sodium and protein is associated with an increased mortality risk, allegedly due to poor nutritional status. These findings support the guidelines that advocate a lower sodium intake, while highlighting the importance of recognizing overall nutritional status among older adults.