In a large population-based observational study with a long 25-years follow-up, scientists at the National Heart Lung and Blood Institute analyzed links between serum sodium levels — which go up when fluid intake goes down — and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges.
It is known that some people age faster than others, some people live into old age disease-free, while others develop age-related chronic diseases.
With a rapidly aging population and an emerging chronic diseases epidemic, finding mechanisms and implementing preventive measures that could slow down the aging process has become a new challenge for biomedical research and public health.
In mice, lifelong water restriction shortens the lifespan and promotes degenerative changes.
“In the study, we aimed to evaluate pro-aging effects of mild subclinical hypohydration,” said lead author Dr. Natalia Dmitrieva, a researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute, and her colleagues.
“We define hypohydration as a state in which water conservation mechanisms, including the secretion of antidiuretic hormone and renal urine concertation, are activated when low water intake or high water loss result in decreased body water content and elevated plasma tonicity.”
“Our hypothesis was inspired by previous mouse studies in which lifelong water restriction, increasing serum sodium by 5 mmol/l, shortened the mouse lifespan by 6 months which corresponds to about 15 years of human life.”
“The shortened life span was accompanied by accelerated degenerative changes within multiple organ systems of the chronically hypohydrated mice.”
In the study, the authors performed a cohort analysis of data from 11,255 participants of the Atherosclerosis Risk in Communities study with middle-age enrollment (45-66 years) and 25 years follow-up.
To allow for a fair comparison between how hydration correlated with health outcomes, they excluded adults who had high levels of serum sodium at baseline check-ins or with underlying conditions, like obesity, that could affect serum sodium levels.
They then evaluated how serum sodium levels correlated with biological aging, which was assessed through 15 health markers.
This included factors, such as systolic blood pressure, cholesterol, and blood sugar, which provided insight about how well each person’s cardiovascular, respiratory, metabolic, renal, and immune system was functioning.
They also adjusted for factors, like age, race, biological sex, smoking status, and hypertension.
The team found that adults with higher levels of normal serum sodium — with normal ranges falling between 135-146 milliequivalents per liter (mEq/l) — were more likely to show signs of faster biological aging.
This was based on indictors like metabolic and cardiovascular health, lung function, and inflammation.
For example, adults with serum sodium levels above 142 mEq/l had a 10-15% associated increased odds of being biologically older than their chronological age compared to ranges between 137-142 mEq/l, while levels above 144 mEq/l correlated with a 50% increase.
Likewise, levels of 144.5-146 mEq/l were associated with a 21% increased risk of premature death compared to ranges between 137-142 mEq/l.
Similarly, adults with serum sodium levels above 142 mEq/l had up to a 64% increased associated risk for developing chronic diseases like heart failure, stroke, atrial fibrillation and peripheral artery disease, as well as chronic lung disease, diabetes, and dementia.
Conversely, adults with serum sodium levels between 138-140 mEq/l had the lowest risk of developing chronic disease.
“People whose serum sodium is 142 mEq/l or higher would benefit from evaluation of their fluid intake,” Dr. Dmitrieva said.
“Most people can safely increase their fluid intake to meet recommended levels, which can be done with water as well as other fluids, like juices, or vegetables and fruits with a high water content.”
“The National Academies of Medicine, for example, suggest that most women consume around 6-9 cups (1.5-2.2 l) of fluids daily and for men, 8-12 cups (2-3 l).”
The findings were published today in the journal eBioMedicine.
Natalia I. Dmitrieva et al. Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality. eBioMedicine, published online January 2, 2023; doi: 10.1016/j.ebiom.2022.104404