sulbutiamine moleculeSulbutiamine Overview

Sulbutiamine, chemically isobutyryl thiamine disulfide,  is a fat soluble vitamin B1 derivative that was developed in Japan to treat vitamin B1 deficiency beriberi. Sulbutiamine is superior to thiamine, regular vitamin b1, as it crosses the blood brain barrier with ease, probably due to its lipophilicity.

Sulbutiamine is used off label for the  treatment of asthenia and fatigue that is of non muscular origin, i.e. perceived fatigue in the brain. Early rodent studies also suggest sulbutiamine can prevent drug induced memory deficits and improve object recognition.

As a nootropic, sulbutiamine is frequently taken on a short term basis to enhance motivation, strengthen memory and support mood. It appears with frequent use a tolerance can develop, so this nootropic is probably best used sparingly.

Other names for Sulbutiamine:

Isobutyrl thiamine disulfide, Arcalion (brand name), Enerion (brand name).

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Important Information

Dosing Sulbutiamine

Limited human studies suggest a dose of 400mg-600mg. (2)(3)(4). It should be noted this study was for diabetic neuropathy and actually failed to show a benefit. Arcalion manufacturers, Serdia Pharma , recommend a maximum daily dose of 600mg per day (5).

Editors note: Finding accurate dosage information on Sulbutiamine is difficult due to the small amount of human trials and even smaller number of trials found in English. As such the optimal dose is not known.Anecdotal evidence suggests people taking between 200mg-600mg per day in a single dose. could be best. Sulbutiamine is fat soluble so be sure to take with a food rather than an empty stomach.

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Sulbutiamine Absorption

Sulbutiamine is lipid soluble and is thought to more readily cross the blood brain barrier than thiamine alone. One rodent study taking place over 14 days involved injections of either saline, sulbutiamine (52mg/kg) or thiamine (50mg/kg) to measure absorption rates. Sulbutiamine injection was found superior to thiamine injection at raising brain levels of thiamine triphosphate and serum levels of thiamine diphosphate, monophsphate and triphosphate were roughly doubled when compared to standard thiamine injection (1).

Sulbutiamine Benefits

Sulbutiamine and Fatigue

Clinical research exists to support the notion that Sulbutiamine can reduce fatigue in certain disease states. One study involving 58 patients of MS showed a substantial improvement in subjective fatigue levels, with 43 patients (74.13%) patients reporting a “substantial improvement” and a further 10 patients (17.24%) reporting some improvement (6).  A further double blind placebo study involving post-infectious chronic fatigue patients suggested both 400mg or 600mg daily sulbutiamine may reduce fatigue levels, though results were mixed and the authors concluded additional research needs to be done (4).

Sulbutiamine was also shown to reduce psycho-behavioural inhibition during major depressive episodes in a double blind randomised placebo controlled trial. Doses used were 600mg / daily. no direct antidepressive effect was noted, nor were side effects (7).

One large uncontrolled study taking place in India selected 1772 patients known to suffer an infectious disease and symptoms of fatigue (asthenia). To be considered for the study, patients had to have been suffering with asthenia for one month.

Patients were prescribed 400mg of sulbutiamine daily with their breakfast and usual anti-infective medication for 15 days. Baseline asthenic symptoms were reported by self assessment of weakness, sleep disturbance, loss of concentration and sexual dysfunction as either absent, mild, moderate or severe. After 15 days, 51% of participants had their symptoms completely resolved and the number of patients reporting severe, moderate and mild symptoms also decreased significantly (8).

Editors Note: This was a large and uncontrolled study that was confounded with the addition of anti-infective medication. It’s a shame there was no control group.

Sulbutiamine and Memory

Human trials with sulbutiamine appear to be lacking as nothing can be found in the common databases aside from rodent studies. It’s interesting to note that the manufacturers claim that their product has been shown to improve intellectual tiredness and strengthens concentration and memory in students. It’s likely a deal of research remains untranslated and unindexed.

One rodent study demonstrated sulbutiamine was able to improve working memory and spatial memory when deficits are induced by the NMDA antagonist dizocilpine. (9) however not against baseline performance.  The study also found that object recognition was improved in the sulbutiamine group versus control.

Editors note: This study would suggest sulbutiamine carries more of an anti-amnesiac for working and spatial memory as there was no improvement unless the rodents were given cognitive deficits. However sulbutiamine did enhance object recognition vs control in the same study.

A further rodent study compared 300mg/kg of oral sulbutiamine for 10 days vs placebo. Compared to control subjects the experimental group showed improved performance in a level press conditioning test 24 hours after acquisition, suggesting some enhancement of memory (10)

Sulbutiamine Mechanisms of Action

Cholinergic – In rodents, sulbutiamine has been shown to enhance choline uptake in the hippocampus (10) by 10% via HACU.

Dopaminergic – A single rodent study indicates that a single injection of sulbutiamine (12.5mg / kg) results in a significant reduction of dopamine in the cingular cortex and a reduction of DOPAC, a dopamine metabolite, in the prefrontal cortex and cingular cortex (11). Due to the reduction in dopamine, a compensatory increase of D1 receptors occurred in both the prefrontal and cingular cortex. Researchers noted that this effect only takes place following chronic treatment and this compensatory effect shouldn’t occur following a single dose (11). It’s suggested that sulbutiamine metabolite, thiamine triphosphate, could possess a modulator effect on neuronal membranes.

Editors note: The rodent study is particularly fascinating and reveals some of sulbutiamine’s acute and chronic effects. Namely a decrease in dopamine following acute exposure and a compensatory increase in D1 receptors following chronic exposure. It’s possible that these dompaminergic effects originate from sulbutiamine’s effects on glutamate, though further research needs to be done to reveal exactly what’s going on.

Sulbutiamine Safety and Side Effects

Sulbutiamine is largely well tolerated . In one study involving 1772 patients, a dose of 400mg per day produced side effects in 0.6% of people (8).  The most noted effect was nausea (0.3%).  There is one documented case in the literature of a bioplar patient being addicted to sulbutiamine, though it should be noted the patient was on a series of medications and was taking over 600mg per day (12).