Several decades ago, researchers in Japan did a lot of research with vitamin B1 (thiamine), as well as its more lipophilic natural and synthetic analogs such as allithiamine, sulbitiamine, fursultiamine, benfotiamine, etc. The studies found that all forms of B1, but especially the more lipophilic ones, enhances both physical and cognitive function, likely by improving glucose metabolism. Namely, B1 is a co-factor for the rate-limiting enzyme in glucose metabolism known as pyruvate dehydrogenase (PDH), and when organisms receive extra B1 they metabolize glucose better, resulting in more CO2 and less lactate produced. Both lower lactate and higher CO2 are known to enhance muscle function, especially during longer term physical exertion. However, the mechanism of action for B1 improving cognitive function is murkier, though lower lactate and higher CO2 contribute to better cognitive function just like they do for muscle function. Since B1 administration was shown to significantly delay fatigue onset during exercise, the researchers in Japan suspected that neurotransmitters are involved in the effects of B1, yet were unable to conclusively prove such a link back then. Nowadays, we have the so-called “central fatigue” hypothesis, which states that fatigue is driven primarily by elevated brain levels of serotonin, combined with low levels of dopamine. The new study below, also done in Japan (and likely by a team that is an extension of same groups that started the work on B1 in the 1950s), demonstrates that B1, in the form of the more lipophilic version thiamine tetrahydrofurfuryl disulfide (TTFD), robustly increased dopamine release in the brain, which then led to increased wakefulness and physical activity. Personally, I would take this results as an experimental confirmation of the “central fatigue” hypothesis. Byw, TTFD is better known as allithiamine and together with its close relative prosultiamine are the only naturally occurring lipophilic B1 analogs, found predominantly in the bulbs of plants from the garlic family. In fact, the unique odor/taste of the garlic-family plants is due to a large degree to the presence of those two lipophilic B1 analogs. In any event, the dose administered in the study was high, but that was likely because it was done as a bolus single dose. The older Japanese studies demonstrated that one can achieve the same levels in the brain as a large bolus dose by administering lower doses over several days. The current study used a single human-equivalent dose of 7.5mg/kg, which means that one should be able to replicate the study by taking 100mg TTFD/allithiamine daily over a period of 7-8 days.
https://dx.doi.org/10.1016/j.jphyss.2024.100001
https://medicalxpress.com/news/2025-05-vitamin-b1-derivative.html
“…Researchers at the University of Tsukuba have found that thiamine (vitamin B1) tetrahydrofurfuryl disulfide (TTFD), a common thiamine derivative, can induce arousal. TTFD is chemically modified to improve tissue penetration and absorption and is recognized for enhancing motivation for physical activity. Thiamine deficiency has long been a significant health concern, contributing to conditions such as beriberi, which was widespread from the Edo to Meiji periods (1868–1912). The development of thiamine derivatives in the 1950s marked a key advance in treating these deficiencies. Today, such derivatives are commonly used as nutritional supplements to support daily energy, even in modern societies where thiamine deficiency is uncommon. Recent studies have also examined the potential effects of thiamine derivatives on brain function. The research team previously discovered that TTFD increases dopamine levels in the medial prefrontal cortex of rats, thereby boosting physical activity. This rise in dopamine is linked to the activation of brain regions involved in arousal, such as the ventral tegmental area and the locus coeruleus. Based on these findings, the team hypothesized that TTFD administration would promote arousal. To test this hypothesis, the team intraperitoneally administered TTFD to rats and assessed changes in their sleep-wake states and physical activity levels using EEG and electromyography. The results indicate that TTFD administration enhanced physical activity and wakefulness. Future studies will aim to uncover the neural mechanisms behind this effect, potentially demonstrating TTFD’s potential in boosting daily vitality.”
