Increased salt intake therapeutic for orthostatic intolerance syndromes?

A review and meta-analysis showed that increased salt intake led to short-term improvements in orthostatic intolerance (OI) syndromes.

A typical example of OI is orthostatic hypotension (OH), which can be debilitating and entails increased risks of falls, injuries, morbidity, and mortality. [Circulation 1998;98:2290-2295; J Am Coll Cardiol 2015;66:848-860] Despite available therapies for this umbrella of conditions, adverse effects (ie, supine hypertension) have been reported. [Postgrad Med J 2006;82:246-253] “Management of this condition is therefore challenging,” said the researchers.

“Overall, there is paucity of high-quality data supporting a cornerstone recommendation in the management of OI syndromes … [Our findings show that] increased salt intake causes a short-term increase in blood pressure (BP) and time to presyncope during orthostasis [and] improved symptoms of OI,” they added.

Studies were mostly small (n=391 total sample from 14 studies), short-term (<60 minutes to 90 days), and of low methodological quality (only three were randomized, of which one was placebo-controlled). Participants were mostly adults (n=302; mean age 35.6 years, 60 percent female), while the rest were children. Participants either had a history of syncope/near-syncope (74 percent), OI, OH, or orthostatic tachycardia (OT; 17 percent), or postural OT syndrome (POTS; 7 percent). Salt supplements were given either orally (table salt or slow sodium tablets 1.2–10.5 g) or via IV infusions (6.3–9 g). [Am J Med 2020;133:1471-1478.e4]

Analysis of five studies revealed that greater salt intake led to increased orthostatic tolerance or time to presyncope by 1.57 minutes in individuals with OH or syncope.

In six studies, after a mean follow-up of 44.3 days, 62 percent had improved or resolved symptoms after increased salt intake. In the only placebo-controlled trial (n=20), after 8 weeks, symptom improvements were greater among those who had salt supplements vs placebo (8/10 vs 3/10; relative risk, 2.67).

In another set of six studies evaluating OH, OT, POTS, and syncope, higher salt intake was tied to a small increase in seated or supine systolic BP (1.03 mm Hg).

Analysis of three studies evaluating participants with syncope or OH revealed a 12.27-mm Hg increase in mean change in head-up tilt or standing systolic BP following increased salt intake.

In four studies, mean change in head-up tilt or standing heart rate dropped by nearly 4 beats/min in individuals with syncope or OT. “[T]his reduction in heart rate [may represent] the pressor effect of increased salt, which results in a lesser drop in orthostatic BP, thus resulting in less of a rebound tachycardia,” explained the researchers. “These may suggest a preferential effect of salt intake on orthostatic [than] supine BP, potentially related to the effect of salt on increasing both circulating intravascular volume and increasing baroreceptor sensitivity and peripheral vascular resistance.”

The incidence of adverse events was low, with only one study reporting poor tolerance in two of 30 patients, and another reporting nausea in 10 patients who took salt capsules.

“[However, our findings highlight] an absence of evidence, rather than evidence of absence, of the long-term clinical benefit of increased salt intake in OI syndromes (eg, on incidence of recurrent falls),” the researchers pointed out.

Also, despite guideline recommendations¹ of increased salt intake for managing OI syndromes, the cardiovascular (CV) risks of high salt intake should not be discounted. Variations in the amounts of salt recommended (6–10 g/day) should also be taken into context.

Larger and longer-term trials are thus warranted to ascertain the efficacy, safety, and CV effect of increased salt intake (including the optimal amount) in relevant populations. Older adults should also be evaluated, as most of the studies involved younger participants. “As many older adults with OH would also be recommended low-salt diets (especially those with co-existing hypertension or heart failure), there is clinical uncertainty about the risk-benefit ratio of long-term high-salt diets,” they added.