Sodium in Effervescent Solutions May Be Associated With Increased Cardiovascular Risk

December 10, 2013

Warning: The maximum daily dose of a single dispersible medication may itself contain more sodium than is recommended from all sources in a day.

Recent campaigns to increase consumer awareness of the dangers of excessive sodium intake and efforts to reduce the salt content of thousands of processed foods may not have had a significant impact on the burden of diseases that are directly linked to sodium consumption, and hypertension in particular. By one estimate, reducing sodium intake in the United States to 2.3 g/d (1 teaspoonful) could prevent 11 million cases of incident hypertension.1

The National Salt Reduction Initiative (NSRI) was established several years ago with a goal to reduce American’s dietary sodium intake by 20% over 5 years. As part of this initiative, food manufacturers have been mandated to disclose sodium content on food labels to increase consumer awareness of sources of dietary sodium. Physicians and patients alike, however, remain largely uninformed about pharmaceutical sources of sodium that could significantly contribute to cardiovascular risk. There is no mandate that directs manufacturers of drugs to report sodium content in their labeling. As a result, the maximum daily dose of a single medication may itself contain more sodium than is recommended from all sources in a day.

A recent nested case-control study published in the British Medical Journal was designed to determine whether patients taking sodium-containing formulations of effervescent, dispersible, and soluble drugs have a higher incidence of cardiovascular events than patients taking non-sodium formulations of the same drugs. Examples of sodium-containing medications included soluble acetaminophen, effervescent aspirin, soluble ibuprofen, calcium carbonate (Alka-Seltzer), and effervescent metoclopramide/aspirin, many of which are available over the counter.

Using the UK Clinical Practice Research Datalink cohort, almost 1.3 million patients were followed for a mean of 7.2 years to determine the incidence of the primary composite outcome of non-fatal myocardial infarction, stroke, or vascular death. After matching controls and cases 1:1, there was an adjusted OR of 1.16 (95% CI, 1.12-1.21) for the primary endpoint for individuals who consumed these sodium-containing solutions. There was also a significant increase in the adjusted ORs for non-fatal stroke (adj. OR = 1.22), all-cause mortality (adj. OR = 1.28), and hypertension (adj. OR = 7.18). The authors note that the increased risk of stroke was most likely due to the associated increased risk of hypertension.

This large observational study suggests that hidden sources of sodium, such as pharmaceuticals of the type evaluated here, may contribute to worse cardiovascular outcomes and to a large increase in the odds for incident hypertension. The message in these results is 3-fold: (1) Physicians must be aware of the sodium content of these and similar solutions; (2) patients should also be made aware of both prescription and over-the-counter formulations with high sodium content; and (3) physicians and patients together should weigh the risk to benefit ratio of such medications before using or prescribing them.


George J, Majeed W, Mackenzie IS, MacDonald TM, Wei L. Association between cardiovascular events and sodium-containing effervescent, dispersible, and soluble drugs: nested case-control study. BMJ 2013; 347 doi: .