Is high salt intake inducing obesity via production of cortisol? A novel working hypothesis and pilot study

Abstract

Purpose: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal.

Methods: Eight participants (age 30.5 ± 9.8 years [mean ± SD], 50% female), consumed high salt (3.82 g; 1529 mg sodium) and low salt (0.02 g; 9 mg sodium) meals in a randomized cross-over design.

Results: Urinary and salivary cortisol and plasma adrenocorticotropic hormone (ACTH) demonstrated order effects. When high salt was given second, there was a peak above baseline for urinary cortisol (26.3%), salivary cortisol (9.4%) and plasma ACTH (4.1%) followed by a significant decline in each hormone (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η² = 0.569; treatment*time, F[12, 24] = 2.668, p = 0.020, partial η² = 0.572; treatment*time, F[12, 24] = 2.580, p = 0.023, partial η² = 0.563, respectively), but not when high salt was given first (p > 0.05 for all).

Conclusion: These intriguing findings provide partial support for our hypothesis and support a need for further research to elucidate the role of high salt intake in cortisol production and, in turn, in the aetiology of obesity.

Trial registration number: ACTRN12623000490673; date of registration 12/05/2023; retrospectively registered.

Keywords: ACTH; Cortisol; Obesity; Salt; Salt intake; Sodium.

Fig. 1

Study design on participants' second and third visits. Saliva, blood, and urine samples and HR and BP measurements were collected every 20 min (long arrows) from 1300 to 1700. Additional saliva and blood (but not urine) samples and HR and BP measurements were collected at 10-min intervals (short arrows) during the first hour after ingestion of the test meals. HR heart rate, BP blood pressure, b.w. body weight

Fig. 2

Urinary sodium in participants (n = 8) who consumed high and low salt test meals in a crossover design. Log₁₀ urinary sodium data are shown in a (treatment*time, F[9, 36] = 3.264, p = 0.005, partial η² = 0.449). For illustrative purposes, b shows data as a proportion of pre-treatment. The timing of the test meals is indicated by the arrow. Data are mean (± SEM). ^a,bIndicates p < 0.05 within the low salt condition

Fig. 3

Urinary cortisol in participants who consumed high and low salt test meals in a crossover design. Due to a significant effect of order (treatment*time*order, F[9, 36] = 3.792, p = 0.002, partial η² = 0.487), separate figures are shown for those who had high salt first (a and c; n = 4) and high salt second (b and d; n = 4). When high salt was second, there was a significant log₁₀ urinary cortisol response (treatment*time, F[9, 18] = 2.641, p = 0.038, partial η² = 0.569; b, but not when high salt was first (treatment*time, (F[9, 18]) = 1.517, p = 0.216, partial η² = 0.431; a. For illustrative purposes, c and d show data as a proportion of pre-treatment. The timing of the test meals is indicated by the arrow. Data are mean (± SEM). ^a,bIndicates p < 0.05 within the high salt condition

Fig. 4

Salivary cortisol in participants who consumed high and low salt test meals in a crossover design. Due to a significant effect of order (treatment*time*order, F[12, 48] = 2.118, p = 0.033, partial η² = 0.346), separate figures are shown for those who had high salt first (a and c; n = 4) and high salt second (b and d; n = 4). When high salt was second, there was a significant response in log₁₀ salivary cortisol (treatment*time, F[12, 24] = 2.668, p = 0.020, partial η² = 0.572; b, but not when high salt was first (treatment*time, F[12, 24] = 1.213, p = 0.330, partial η² = 0.377; a. For illustrative purposes, c and d show data as a proportion of pre-treatment. The timing of the test meals is indicated by the arrow. Data are mean (± SEM). ^a,bIndicates p < 0.05 within the high salt condition; ^c,dindicates p < 0.05 within the low salt condition

Fig. 5

Plasma ACTH in participants who consumed high and low salt test meals in a crossover design. Due to a significant effect of order (treatment*time*order, F[12, 48] = 3.431, p = 0.001, partial η² = 0.462), separate figures are shown for those who had high salt first (a and c; n = 4) and high salt second (b and d; n = 4). When high salt was second, there was a significant response in square root plasma ACTH (treatment*time, F[12, 24] = 2.580, p = 0.023, partial η² = 0.563; b, but not when high salt was first (treatment*time, F[12, 24] = 1.398, p = 0.234, partial η² = 0.411; a. For illustrative purposes, c and d show data as a proportion of pre-treatment. The timing of the test meals is indicated by the arrow. Data are mean (± SEM). ^a,bIndicates p < 0.05 within the high salt condition