Practice Point: Consider a narrower range of “normal” for serum sodium concentration.
EBM Pearl: Do not leap from association to causation based only on observational data.
Has “drink more water” ever been one of your New Year’s Resolutions? A study published in the journal eBioMedicine sponsored by The Lancet assessed the relationship between serum sodium, a marker of hydration, and the risk of premature aging, chronic disease development, and mortality. Given evidence that chronic water restriction in mice leads to shorter lifespans, the authors hypothesized that hydration has an integral effect on aging and that optimal hydration could potentially slow down the aging process.
Researchers analyzed data from the Atherosclerosis Risk in Communities study – an ongoing prospective cohort of more than 15,000 adults who were enrolled between 1985 and 1987 (aged 45-66 years at enrollment) and followed every three years for up to 25 years. The average fasting serum sodium level obtained from visit one and two was used as a proxy for hydration status. The speed of aging was assessed in terms of a biological age calculation, the development of chronic disease, and all-cause mortality.
Biological age was calculated with a formula that integrated 15 age-related proxies for health, such as systolic blood pressure, forced expiratory volume, and serum markers of metabolism and inflammation.
Participants excluded from the analysis included those with serum sodium levels outside of the reference range (135-146 mmol/l), blood glucose levels greater than 140 mg/dL, body mass index (BMI) above 35 kg/m2, and those who used blood pressure- or cholesterol-lowering medications.
After exclusions, data from 11,255 participants were analyzed. A serum sodium concentration of 137-142 mmol/l was associated with the lowest mortality rate (26.2%), and increased mortality was noted at both ends of the “normal” range: 135 to 136.5 mmol/l (39.3%) and 144.5 to 146 mmol/l (34.5%). Serum sodium concentration greater than 142 mmol was associated with a 39 percent increase in risk of chronic disease (hazard ratio 1.39) and a 10 to 15 percent increase in the likelihood of having a biological age that was older than chronological age. This risk increased to 50 percent in people with serum sodium levels higher than 144 mmol/l. Notably, older biologic age was associated with an increased risk of chronic disease (hazard ratio 1.7) and premature mortality (hazard ratio 1.59).
Feeling thirsty yet?
Although the evidence from this study supports an association between elevated sodium concentration and accelerated aging, it also shows that low serum sodium levels may be problematic. What’s more, it’s a pretty big leap to assume that a normal serum sodium concentration can be used as a proxy for hydration status given that volume status does not always correlate with serum sodium. It’s also unclear which way the association actually goes – does higher or lower sodium concentration result in chronic disease, or does chronic disease lead to changes in sodium levels?
The exclusion of participants with abnormal sodium levels, diabetes, obesity, or those who are taking medication to control hypertension or hyperlipidemia was an attempt to control for confounders. However, this limits the generalizability of the results. Furthermore, the researchers did not exclude other confounders which might account for the increased risk seen in individuals who had serum sodium concentrations at the edges of the normal range.
This observational study certainly does not prove a causal link. The results could facilitate discussion about hydration practices with patients, but otherwise its impact on clinical practice is slim. We’re not saying hydration isn’t a good idea – just that this particular study does not provide the evidence for it.
The real takeaway from this study may be that the normal range for serum sodium concentration may be too wide. It is not clear, however, what interventions this information might suggest.
For more information, see the topic Dehydration and Hypovolemia in Adults in DynaMedex.
Reference: EBioMedicine. 2022 Dec 13 early online
