Electrolyte Biomarkers: Sodium

Optimal Takeaways

Sodium is an essential mineral. It is crucial for nerve transmission, cell membrane transport, acid-base balance, and osmotic pressure. Sodium levels are regulated by a complex system involving hormones, enzymes, fluid balance, and kidney function. The equilibrium between kidney retention and the excretion of sodium and water helps regulate blood pressure. Low sodium is associated with fluid overload, insufficient intake, excess losses, and certain medications. High sodium is associated with dehydration, excess intake, increased aldosterone, and certain medications.

Standard Range: 135 - 146 mEq/L (135 – 146 mmol/L)

The ODX Range: 137 - 142 mEq/L (137 – 142 mmol/L)    

Low levels of serum sodium are associated with hyperglycemia (Dmitrieva 2022), insufficient intake, overhydration or fluid retention, edema, gastrointestinal losses, congestive heart failure, Addison disease, and excess ADH or natriuretic hormone. Medications that decrease sodium levels include diuretics, ACE inhibitors, NSAIDs, carbamazepine, heparin, sulfonylureas, vasopressin, and tricyclic antidepressants (Pagana 2021). The combined use of benzodiazepines and thiazide diuretics significantly increases risk of hyponatremia. Low levels are also associated with diabetes which is an independent risk factor for hyponatremia (Liamis 2013).

High levels of sodium are associated with dehydration, excess sodium intake, diabetes insipidus (insufficient ADH), Cushing syndrome, hyperaldosteronism, thermal burns, recent surgery, trauma, or shock. Excess sweating can increase serum sodium by decreasing free body water and concentrating sodium in the blood, though some sodium is also lost through sweating. Medications can increase sodium levels including anabolic steroids, corticosteroids, antibiotics, laxatives, methyldopa, and estrogen (Pagana 2021). High serum sodium is also associated with hypertension (Wannamethee 2016) and decreased estimated glomerular filtration rate (Nakajima 2016).

Overview

Sodium is a major electrolyte and the most abundant cation in the blood and extracellular spaces. It is involved in acid-base balance, nerve transmission, and the maintenance of osmotic pressure, blood pressure, and cell membrane ion transport. Excess sodium intake may contribute to hypertension and increased urinary calcium excretion, while insufficient sodium and low serum levels can cause hypotension, fatigue, weakness, nausea, and muscle cramping. Some of the negative effects of excess sodium intake may be due to sodium chloride, but not other forms of sodium such as sodium ascorbate, citrate, or bicarbonate (Gaby 2017). For example, early research demonstrated a hypertensive response to sodium chloride (common table salt) but not sodium bicarbonate (McCallum 2015).

Serum sodium concentration depends on how much sodium and fluid are consumed and then excreted by the kidneys. Hormonal control of sodium levels involves aldosterone and antidiuretic hormone (vasopressin). Aldosterone retains sodium by decreasing its excretion, which increases serum levels. Aldosterone also causes the excretion of potassium, lowering its level in the blood. The antidiuretic hormone increases fluid retention and therefore decreases serum sodium by way of dilution (Pagana 2021).

Data review of 100,649 adults undergoing routine health checkups found that a sodium of 141 mEq/L or above was associated with significantly higher systolic and diastolic blood pressure compared to 138-139 mEq/L in a data review of 100,649 adults undergoing routine health checkups. Levels above 145 mEq/L were associated with greater mortality. Salt sensitivity and hypertensive response were magnified in the presence of insulin resistance and metabolic syndrome (Oh 2013).

In another review of health checkups, records revealed that a serum sodium of 144 mEq/L or greater was associated with significantly higher blood pressure (130/85 mmHg or above) and significantly reduced eGFR below 60 ml/min/1.73 m2 (Nakajima 2016).

In men 60-79 years old, a prospective study found that sodium below 138 mEq/L or a level of 145 mEq/L or above had a significantly greater risk for major cardiovascular events and mortality. The study confirms previous research observing increased mortality with sodium in the low normal range of 135-137 mEq/L (Wannamethee 2016).

Using serum sodium as a proxy for hydration status, analysis of data from the Atherosclerosis Risk in Communities (ARIC) study found that sodium above 142 mmol/L was associated with increased biological age and increased risk of developing a chronic disease by 39%. Sodium above 144 mmol/L increased the risk of premature mortality by 21%. Researchers attribute the associated negative effects to underhydration. The lowest mortality was observed in subjects with serum sodium of 137-142 mmol/L. All-cause mortality increased by 71% with serum sodium of 135-136.5 mmol/L (Dmitrieva Dec 13, 2022).

Further analysis of the ARIC data in older individuals aged 70-90 found that serum sodium above 143 mmol/L was associated with a 1% body weight water deficit. The risk of left ventricular hypertrophy increased by 62% with serum sodium of 142.5-143 mmol/L and 107% with sodium above 143 mmol/L (Dmitrieva 2022).

References

Dmitrieva, Natalia I et al. “Middle age serum sodium levels in the upper part of normal range and risk of heart failure.” European heart journal vol. 43,35 (2022): 3335-3348. doi:10.1093/eurheartj/ehac138

Dmitrieva, Natalia I et al. “Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality.” EBioMedicine, 104404. 13 Dec. 2022, doi:10.1016/j.ebiom.2022.104404

Gaby, Alan R. Nutritional Medicine. Fritz Perlberg Publishing, 2017.

Oh, Se Won et al. “Small increases in plasma sodium are associated with higher risk of mortality in a healthy population.” Journal of Korean medical science vol. 28,7 (2013): 1034-40. doi:10.3346/jkms.2013.28.7.1034

Liamis, George et al. “Electrolyte disorders in community subjects: prevalence and risk factors.” The American journal of medicine vol. 126,3 (2013): 256-63. doi:10.1016/j.amjmed.2012.06.037

McCallum, Linsay et al. “The hidden hand of chloride in hypertension.” Pflugers Archiv: European journal of physiology vol. 467,3 (2015): 595-603. doi:10.1007/s00424-015-1690-8

Nakajima, Kei et al. “The association of serum sodium and chloride levels with blood pressure and estimated glomerular filtration rate.” Blood pressure vol. 25,1 (2016): 51-7.    doi:10.3109/08037051.2015.1090711

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Wannamethee, S G et al. “Mild hyponatremia, hypernatremia and incident cardiovascular disease and mortality in older men: A population-based cohort study.” Nutrition, metabolism, and cardiovascular diseases : NMCD vol. 26,1 (2016): 12-9. doi:10.1016/j.numecd.2015.07.008