Benefits
Fatigue after infection: an early effect that did not last
In a randomized, double-blind trial of 326 people with chronic fatigue after an infection, 400 or 600 mg a day for 28 days did not differ from placebo overall; women on 600 mg had less fatigue on day 7, but not by day 28. A large uncontrolled observational study in India reported full symptom resolution in about half of 1,772 patients when sulbutiamine was added to anti-infective treatment.
Sexual function scores in one uncontrolled study of 20 men
In a small study without a placebo group, 20 men with erection problems linked to psychological causes took Enerion (sulbutiamine) for 30 days; 16 improved, and in those 16 the average erectile function score (IIEF) rose from 17.5 to 24.8. The dose was not given in the abstract and the result has not been replicated, so it says little about sulbutiamine for sexual health.
Fatigue scores in people with multiple sclerosis
In an uncontrolled 2-month observational study of 26 people with multiple sclerosis, 400 mg a day lowered Fatigue Impact Scale scores from 77 to 60.5. Improvement was seen only in people who were also on disease-modifying treatment, and there was no placebo group, so this is an early signal rather than an established use.
Memory and attention: mouse data and one add-on trial
In mice, long-term sulbutiamine increased hippocampal choline uptake by 10% and improved performance on a partial learning task. In a randomized, double-blind trial in early Alzheimer's disease, adding 400 to 600 mg a day to donepezil improved episodic memory, attention and daily activities more than donepezil alone, according to a review. Human memory trials are few.
Brain cell protection in laboratory and rat stroke models
In rats with an induced stroke, sulbutiamine improved survival, reduced neurological deficit scores and limited nerve cell loss, and it protected cultured nerve cells deprived of oxygen and glucose, partly by lowering reactive oxygen species. Earlier cell studies found similar protective effects. None of this has been tested in people.
Less emotional and behavioural slowing, studied as an antidepressant add-on
In an 8-week double-blind trial, inpatients with major depression on the antidepressant clomipramine also took sulbutiamine 600 mg/day or placebo. Depression and anxiety scores improved equally in both groups, so it had no antidepressant effect, but the sulbutiamine group reported less disability from affective, cognitive and behavioural slowing, with no mania or suicide attempts.
Mechanism of action
Better brain entry than thiamine
Sulbutiamine is a fat-soluble thiamine disulfide. It raises levels of thiamine and thiamine phosphate esters in the brain, which regular water-soluble thiamine does less readily.
Conversion back to thiamine
In the body the disulfide bond is reduced, giving isobutyryl-thiamine, and the isobutyryl groups are removed to yield thiamine. Its active form, thiamine diphosphate, is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and transketolase, enzymes central to energy metabolism.
Cholinergic effects in mice
Long-term sulbutiamine increased high-affinity choline uptake by 10% in mouse hippocampal neurons, which reviewers link to the memory effects seen in mice. This has not been measured in people.
Dopamine and glutamate receptor changes in rats
In rats, repeated sulbutiamine increased dopamine D1 binding sites in the prefrontal and cingulate cortex and reduced kainate (glutamate) binding sites, while a single dose lowered dopamine metabolites. How this relates to effects in people is unknown.
Clinical trials
Randomized, double-blind, parallel-group trial in general practice: sulbutiamine 400 mg/day, 600 mg/day or placebo for 28 days (Tiev et al. 1999, Rev Med Interne).
326 adults with chronic post-infectious fatigue (106 on 400 mg, 111 on 600 mg, 109 on placebo); 315 completed.
Overall, fatigue (measured mainly with the MFI scale) did not differ significantly between groups. Women on 600 mg had less fatigue on day 7 (P<0.01), but no persistent effect was seen on day 28, and the authors said the early finding needs confirmation.
Single-group study without a control group: sulbutiamine 400 mg once daily for 2 months (Sevim et al. 2017, Mult Scler Relat Disord).
26 people with multiple sclerosis (18 women, 8 men, aged 18 to 57) with fatigue as a main symptom, Fatigue Impact Scale over 20, low depression scores and no relapse in the prior 3 months.
Total Fatigue Impact Scale scores fell from 77 to 60.5 (p<0.01), with improvement on the physical, cognitive and psychosocial subscales. Improvement was seen only in people also on disease-modifying treatment. No serious adverse events were reported, and there was no placebo group.
Uncontrolled 30-day study of Enerion (sulbutiamine), published in Russian; the dose is not given in the abstract (Dmitriev et al. 2005, Urologiia).
20 men with psychogenic (functional) erectile dysfunction.
Erectile function improved in 16 of 20 men, and in those 16 the mean IIEF score rose from 17.5 to 24.8 points. Penile arterial blood flow improved in 3 of 6 men with arterial problems. With no control group and no replication, this cannot show that sulbutiamine caused the change.
8-week multicentre, randomized, double-blind, placebo-controlled trial of sulbutiamine 600 mg/day added to clomipramine 75 to 150 mg/day (Lôo et al. 2000, Encephale).
Inpatients with a DSM III-R major depressive episode.
Depression (MADRS), anxiety (HAM-A) and global (CGI) scores improved similarly in both groups, so sulbutiamine had no antidepressant effect. On disability and visual analogue scales, the sulbutiamine group was significantly less impaired by affective, cognitive, emotional and behavioural slowing. Safety was similar in both groups, with no mania or suicide attempts.