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May 2, 2017
How the body regulates salt levels
At a Glance
- A series of experiments with men in a space flight program and mice overturns long-held beliefs about thirst and reveals how the body controls its salt and water balance.
- The complex interplay of mechanisms has important effects on hormones, metabolism, and possibly development of disease.
Sodium chloride, commonly called dietary salt, is essential to our body. But a high salt intake can raise blood pressure, which can damage the body in many ways over time. High blood pressure has been linked to heart disease, stroke, kidney failure, and other health problems. However, not everyone is equally sensitive to high levels of salt.
Researchers have long believed that the way the level of salt inside our bodies is controlled is fairly straightforward: when levels are too high, our brains are stimulated to make us thirsty. We drink more and excrete more urine, through which the body expels excess salt.
To gain insight into this process, a team led by Dr. Jens Titze at the University of Erlangen-Nuremberg in Germany took the opportunity to study men participating in a simulated space flight program. Between 2009 and 2011, they tightly controlled the daily salt intake of 10 men simulating a flight to Mars: four in a 105-day pre-flight phase and six others for 205 days. The men were given 12 grams of salt per day, 9 g/day, or 6 g/day for 30–60 days. The researchers collected all the men’s urine for testing.
The scientists were surprised to find that, whatever the level of salt consumed, sodium was stored and released from the men’s bodies in roughly weekly and monthly patterns. The team uncovered similar rhythms for the hormones aldosterone, which regulates sodium excretion from the kidney, and glucocorticoids, which help regulate metabolism.
Titze, now at Vanderbilt University Medical Center, continued to examine the long-term control of sodium and water balance in the men. To better understand the mechanisms at work, his team also performed experiments in mice. Their latest results appeared in two papers on May 1, 2017, in the Journal of Clinical Investigation. The work was funded in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Changing salt intake affected levels of both aldosterone and glucocorticoids, the hormones found to rhythmically control the body’s salt and water balance. These, in turn, had a number of interesting effects in the body. Increasing salt intake increased sodium excretion, but also unexpectedly caused the kidney to conserve water. Excess sodium was thus released in concentrated urine. This method of protecting the body’s water was so efficient that the men actually drank less when their salt intake was highest.
These results show that the body regulates its salt and water balance not only by releasing excess sodium in urine, but by actively retaining or releasing water in urine. The advantage of this mechanism is that the long-term maintenance of body fluids isn’t as dependent on external water sources as once believed.
The researchers found that the kidney conserves or releases water by balancing levels of sodium, potassium, and the waste product urea. This may be what ties glucocorticoid levels to salt intake. A high salt diet increased glucocorticoid levels, causing muscle and liver to burn more energy to produce urea, which was then used in the kidney for water conservation. That also led the mice to eat more. These salt-driven changes in metabolism may thus partly explain why high salt diets have been linked to diabetes, heart disease, and other health problems that can result from the condition known as metabolic syndrome.
“We have always focused on the role of salt in arterial hypertension. Our findings suggest that there is much more to know—a high salt intake may predispose to metabolic syndrome,” Titze says. More work will be needed to better understand these mechanisms.
—by Harrison Wein, Ph.D.
- Scientists Identify Thirst-Controlling Neurons
- Shaking Out Clues to Autoimmune Disease
- High Salt Detected by Sour and Bitter Taste Cells
- The Health Benefits of Cutting Salt
- Sodium/Potassium Ratio Linked to Cardiovascular Disease Risk
- Metabolic Syndrome
References: Increased salt consumption induces body water conservation and decreases fluid intake. Rakova N, Kitada K, Lerchl K, Dahlmann A, Birukov A, Daub S, Kopp C, Pedchenko T, Zhang Y, Beck L, Johannes B, Marton A, Müller DN, Rauh M, Luft FC, Titze J. J Clin Invest. 2017 May 1;127(5):1932-1943. doi: 10.1172/JCI88530. Epub 2017 Apr 17. PMID: 28414302.
High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T, Lantier L, LaRocque LM, Marton A, Neubert P, Schröder A, Rakova N, Jantsch J, Dikalova AE, Dikalov SI, Harrison DG, Müller DN, Nishiyama A, Rauh M, Harris RC, Luft FC, Wassermann DH, Sands JM, Titze J. J Clin Invest. 2017 May 1;127(5):1944-1959. doi: 10.1172/JCI88532. Epub 2017 Apr 17. PMID: 28414295.
Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); German Federal Ministry for Economics and Technology/DLR Forschung unter Weltraumbedingungen; American Heart Association; Renal Research Institute; TOYOBO Biotechnology Foundation; Interdisciplinary Center for Clinical Research Erlangen; and Deutsche Forschungsgemeinschaft.