Benefits
Raises blood thiamine after an oral dose
In healthy adults, a single 100 mg oral dose of TTFD raised blood thiamine to a peak almost 10 times the starting level. Absorption was described as complete at doses up to 180 mg and did not fall off as the dose rose. The lead author worked at Takeda, a Japanese drug company.
Blood thiamine compared with thiamine salts and benfotiamine
In healthy Korean men, a multivitamin with fursultiamine gave more than 300% higher plasma thiamine exposure than one with thiamine nitrate, and total exposure similar to a benfotiamine product. In a 7-person study, benfotiamine raised blood thiamine more than fursultiamine did. Higher blood levels have not been shown to bring extra benefit in people who are not low in B1.
Thiamine status markers when B1 status is low
An older report found that oral allithiamines raised thiamine in blood, red cells and spinal fluid, and returned red cell transketolase (a B1 status marker) to normal in alcoholics with thiamine deficiency, while oral thiamine salts did not. Thiamine deficiency needs medical care; suspected severe deficiency is an emergency treated in hospital.
Exercise performance and fatigue markers in healthy adults
Three small placebo-controlled crossover trials gave about 1,000 mg a day of TTFD or allithiamine for 4 to 7 days (one also added pantethine) and found no change in cycling time trials, oxygen uptake, muscle strength or blood lactate. One 9-person study of 4 weeks of TTFD reported lower lactate and ammonia during exercise, but it was small and not clearly blinded.
Open-label studies in patient groups
Two uncontrolled studies are context only. In 44 hospital patients in Indonesia with nerve damage from poor nutrition, 34 regained some motor function on TTFD. In a 12-week open trial of 100 mg/day fursultiamine in people with Alzheimer's disease, the authors reported a mild benefit, with cognitive gains only in mildly impaired patients. Without control groups, neither shows that TTFD caused the change.
Mechanism of action
Absorbed by a different route than thiamine salts
Plain thiamine salts are taken up by a carrier in the gut that limits how much can be absorbed at once. Allithiamine and TTFD are truly lipid-soluble disulfides, so they are absorbed by a different route. This is the usual explanation for why blood thiamine rises more after TTFD than after a thiamine salt.
Reduced back to thiamine by the body's thiol systems
In lab tests, the glutathione and thioredoxin systems that cells use to break disulfide bonds reduced fursultiamine and related thiamine disulfides, releasing the open thiol form of thiamine. In gut-lining cells these compounds also protected against induced oxidative stress. These are cell and enzyme findings, not results in people.
Once released, it works as ordinary vitamin B1
After conversion, the thiamine is turned into thiamine diphosphate, the coenzyme form used by transketolase and other energy-metabolism enzymes. In thiamine-deficient mice, allithiamine and plain thiamine raised blood thiamine to similar levels with similar effects on a thiamine-dependent enzyme, suggesting the effect is supplying B1 rather than a unique action.
A different chemical class from benfotiamine
Benfotiamine is an S-acyl thiamine derivative that is practically insoluble in oils and is proposed to be absorbed only after it is dephosphorylated in the gut. Lipid-soluble disulfides such as allithiamine, TTFD and sulbutiamine are absorbed and handled differently, so results for benfotiamine cannot be assumed to apply to them.
Clinical trials
Pharmacokinetic study of oral TTFD (10 mg and 100 mg, with absorption assessed up to 180 mg), subtracting baseline dietary thiamine, led by a researcher at Takeda in Japan. (Kitamori et al. 1993, J Nutr Sci Vitaminol (Tokyo))
Healthy adults (number not given in the abstract).
After 100 mg of TTFD, peak blood thiamine was almost 10 times the baseline level. The authors concluded that even 180 mg was completely absorbed and that the absorbed fraction did not depend on dose. The abstract reports no thiamine salt comparison and no health outcome was measured.
Two randomized, single-dose, two-way crossover pharmacokinetic studies of multivitamin products containing fursultiamine, benfotiamine or thiamine nitrate as the main thiamine source. (Park et al. 2016, Clin Ther)
Healthy Korean men, 24 per study.
Total thiamine exposure after fursultiamine was slightly higher than after benfotiamine (plasma AUC ratio 116.6%, hemolysate 137.5%), but the 90% confidence interval for summed exposure fell within the usual bioequivalence range. Against thiamine nitrate, plasma thiamine exposure was more than 300% higher with fursultiamine. Single doses only; no clinical outcomes.
Multiple change-over bioavailability study of single 100 mg oral doses of three thiamine derivatives, measuring blood thiamine for 10 hours, 24-hour urine thiamine and red cell transketolase. (Greb et al. 1998, Int J Clin Pharmacol Ther)
7 volunteers.
Benfotiamine gave a faster rise and significantly greater thiamine bioavailability than fursultiamine or thiamine disulfide; thiamine disulfide was lowest. There was no plain thiamine salt arm. This differs from the later Korean study, which found fursultiamine and benfotiamine similar.
Randomized, double-blind, placebo-controlled crossover trial with a 10-day washout; TTFD 1 g/day for 4 days before a graded exercise test and a 2000 m cycling time trial. (Webster et al. 1997, Eur J Appl Physiol Occup Physiol)
14 subjects.
No significant differences in submaximal oxygen uptake, lactate or heart rate. Peak oxygen uptake was 4.12 vs 4.06 L/min (P = 0.83) and 2000 m time 200.9 vs 204.5 s (P = 0.61) for TTFD vs placebo. The authors concluded the thiamin derivative does not influence high-intensity exercise performance.
Double-blind, counterbalanced, crossover trial of oral allithiamine 1 g/day or placebo for 5 days, followed by six sets of knee extension and flexion on an isokinetic dynamometer. (Doyle et al. 1997, Int J Sport Nutr)
15 healthy college students.
No significant differences between allithiamine and placebo in peak torque, mean peak torque, average power or total work, and no difference in blood lactate before, during or after exercise.
Randomized, double-blind, counterbalanced crossover trial of 1 g allithiamin plus 1.8 g of a pantethine and pantothenic acid compound daily for 7 days, before a 50 km ride and a 2000 m time trial. (Webster 1998, Eur J Appl Physiol Occup Physiol)
6 highly trained cyclists.
No significant differences in heart rate, gas exchange, perceived exertion, blood lactate, glucose or free fatty acids. The 2000 m time was 170.7 s with the supplement vs 178.2 s with placebo (P = 0.58). Because a combination was tested, the effect of allithiamin alone cannot be separated.
Three-condition crossover study (placebo, 4 weeks of cycling training, 4 weeks of TTFD described as 10 mg per kg body weight) in random order, each tested with 60 minutes of cycling at 70% of maximal oxygen uptake. (Choi et al. 2013, J Exerc Nutrition Biochem)
9 female university physical education students.
Compared with placebo, the TTFD condition had lower blood lactate during exercise and lower ammonia during exercise and early recovery, and the authors reported lower perceived exertion. The study was very small, blinding was not described, and exercise performance was not measured.
Open trial (no control group) of TTFD in patients admitted to a neurology department in Surabaya, Indonesia. (Djoenaidi et al. 1990, Eur Arch Psychiatry Neurol Sci)
44 patients with nutritional polyneuropathy, which the authors thought was mostly caused by thiamine deficiency.
34 of 44 patients improved in motor function (P < 0.01), with slight restoration of sensation and reflexes (P < 0.1). Of 18 re-examined with nerve tests 3 months later, 6 showed marked improvement. No side effects were seen. Without a control group, the improvement cannot be attributed to TTFD, and these patients were presumed to be low in B1, so the results do not apply to healthy people.