Though benfotiamine is lipid-soluble, it metabolizes quickly, producing high levels of thiamine pyrophosphate (TPP, the active form of thiamine), which then continues to metabolize in the body as usual.  Benfotiamine itself does not accumulate in the body.  The original patent filed in the United States on benfotiamine, Adobe Version of Benfotiamine Patent, included data from LD-50 tests on lab mice (Table III) indicating that benfotiamine is significantly less toxic than common vitamin B-1 (typically, thiamine hydrochloride).  Thiamine hydrochloride has been the subject of much research.  To quote from the European Commission Health and Consumer Protection Directorate General study on the tolerable upper intake level of vitamin B-1, paragraph 3. Hazard Identification:

 

"3.1. Evidence of adverse effects in humans. Orally ingested vitamin B1 has a long history of use as an oral supplement without reported adverse effects. Due to its therapeutic action in some frequently observed clinical syndromes, thiamine hydrochloride has been advised and used over a long period of time. There are no reports of adverse effects of oral thiamine, even at dosages of several hundred milligrams a day (SCOGS, 1978; DHEW, 1979; Marks, 1989).”

The entire EC study is available at:  Tolerability of Thiamine (Vitamin B-1).  Again, vitamin-B-1 has proven safe after decades of public use and benfotiamine has been found to be significantly more tolerable than common vitamin B-1.  Also, there are no known negative interactions between benfotiamine and other supplements or medications.  However, there is information published by Ohio State University in 1996 and by the European Journal of Biochemistry in 2001 indicating thiamine supplementation should be carefully considered in patients undergoing therapy for tumorous forms of CANCER.  These articles address thiamine in general (not specifically benfotiamine) but I find them relevant since benfotiamine is essentially a very effective form of thiamine.  You may access that information here:  OSU Article, EJB Abstract.

Otherwise, I believe there is minimal to nil downside in trying benfotiamine and the individual results have the potential to be quite significant.  Still, it is wise and prudent to monitor your own reactions to any new supplement and adjust your dosage accordingly. In over 7 years I have had 2 or 3 reports of thiamine hypersensitivity and one report of excessive dosing. If you have a known sensitivity to thiamine, you should know that benfotiamine is a very potent metabolic precursor of active thiamine and dose it cautiously if at all. Symptoms of excessive dosing could include a feeling of warmth, weakness, sweating, nausea, restlessness, difficulty breathing, tightness of the throat or even bluish colored skin. If these symptoms occur you should immediately reduce your dosage or stop taking the product.