Does Small Intestinal Bacterial Overgrowth Play a Role in Restless Leg Syndrome?


All told, every patient with RLS in the study had SIBO present, in comparison to general population rates which range from roughly 6% to greater than 15%.

Dr Daniel J Blum

Daniel J. Blum, PhD, DBSM, adjunct clinical instructor, Stanford University department of psychiatry and behavioral sciences, Stanford Center for Sleep Sciences and Medicine

Daniel J. Blum, PhD, DBSM

Small intestinal bacterial overgrowth (SIBO), which is often associated with gut dysbiosis, may be more predominant among patients with restless leg syndrome (RLS), according to new preliminary data presented at SLEEP 2019, June 8-12, in San Antonio, Texas.1

The investigators hypothesized that this incidence of generally rare gut-residing bacteria being over-represented in the gut is associated with RLS, and as such may in some way moderate the observed inter-patient variability in serum iron availability. All told, every patient in the study had SIBO present, in comparison to general population rates which range from roughly 6% to greater than 15%.

Led by Daniel J. Blum, PhD, DBSM, adjunct clinical instructor in the Stanford University department of psychiatry and behavioral sciences and Stanford Center for Sleep Sciences and Medicine, the investigators noted that 7 patients with RLS (3 men, 4 women) have thus far completed the study protocol, all of whom reported Pittsburgh Sleep Quality Index (PSQI) scores ≥5. SIBO was present also present in all of them.

“We’ve observed extremely high rates of small intestinal bacterial overgrowth in the RLS group,” Blum said in a statement.2 “Exploring the relationship between RLS and gut microbial health has the potential to open novel avenues for possible detection, prevention, and treatment for RLS and other sleep disorders.”

Additionally, all of the patients thus far recruited to the Stanford Sleep Center reported moderate to severe symptoms of RLS, as measured by International Restless Legs Scale (IRLS) scores which ranged from 13 to 34 of a possible 40.

Some estimates have suggested that the overall prevalence of SIBO in the general public is unknown and likely underdiagnosed, and a 2010 study from Bures et al. suggested that “according to different studies with the investigation of small sets of clinically healthy people as a control, findings consistent with SIBO were found in 2.5% to 22%.”3

Blum and colleagues wrote that although RLS’s pathogenesis is not completely understood, some patients with RLS have been noted to have a relative state of brain iron deficiency. This, they wrote, seems to bring forth changes in a number of pathways—the adenosinergic, glutamatergic and dopaminergic, specifically—which are involved in the condition.

“Insufficient iron may be secondary to dietary iron deficiency or, potentially, gut inflammation,” they wrote. This hypothesis is still being assessed, and participants to the study are being recruited to the Stanford Sleep Center.

After being enrolled the patients are being grouped into 3 factions: those with RLS and low peripheral iron stores (defined as <50ng/mL and/or transferrin saturation <18%), those with RLS and normal peripheral iron stores, and those with insomnia to serve as a control group. They then complete questionnaires concerning their sleep and SIBO symptoms.

Patients are given Norgen Biotek’s Fecal Swab Collection and Preservation System and Quintron’s SIBO Home Breath Test Kit. The fecal samples are assayed by the University of Minnesota Genomics Center with microbial community profiling evaluated by 16S ribosomal RNA (16S rRNA) gene sequencing protocols, while the SIBO breath samples are evaluated by Aerodiagnostics for hydrogen and methane abnormalities.

For more coverage of SLEEP 2019, click here.


1. Blum DJ, During E, Barwick F, Davidenko P, Zeitzer JM. Restless Leg Syndrome: Does It Start With A Gut Feeling? Presented at: SLEEP 2019. June 8-12, 2019; San Antonio, TX. Abstract 0009.

2. High levels of rare gut bacteria may be linked to restless legs syndrome [press release]. Darien, IL: American Academy of Sleep Medicine; Published June 7, 2019. Accessed June 12, 2019.

3. Bures J, Cyrany J, Kohoutova D, et al. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010;16(24): 2978-2990. doi: 10.3748/wjg.v16.i24.2978.

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