Benfotiamine, thiamine monophosphate chloride and thiamine pyrophosphate chloride, as sources of vitamin B1 added nutritional purposes to food supplements

Thiamine monophosphate chloride and thiamine pyrophosphate chloride The Panel concludes that the bioavailability of thiamine from thiamine monophosphate and thiamine pyrophosphate will be similar to that of thiamine. There have been no toxicological studies carried out with thiamine monophosphate chloride and thiamine pyrophosphate chloride to evaluate reproductive and developmental toxicity, genotoxicity or long term toxicity of thiamine monophosphate chloride and thiamine pyrophosphate chloride. However, given the facts that: •thiamine monophosphate and thiamine pyrophosphate are endogenous metabolites of thiamine, •these forms are interconvertible, •thiamine monophosphate and thiamine pyrophosphate are naturally present in the diet, •absorption of thiamine monophosphate and thiamine pyrophosphate is preceeded by their conversion to thiamine, •the EVM defined a guidance level of 100 mg/day of supplemental vitamin B1, the Panel concludes that the use of thiamine monophosphate and thiamine pyrophosphate as a source of thiamine at the proposed levels of use in food supplements is not of safety concern, provided that the maximum of 100 mg/day of supplemental vitamin B1 holds for the sum of all thiamine sources. Benfotiamine Benfotiamine is absorbed much better than water soluble thiamine salts. Maximum plasma levels of thiamine are about 5-fold higher after benfotiamine intake and the bioavailability is about 3.6 times as high as that of thiamine hydrochloride and better than that of other lipophilic thiamine derivatives. The increase in relative bioavailability is most significant in muscle (5-fold greater incorporation) and brain (25-fold increase), but thiamine from benfotiamine is also 10-40% better incorporated in other organs, such as liver and kidney. The Panel concludes that the bioavailability of thiamine from benfotiamine is higher than that from other sources. For benfotiamine several human clinical studies at dose levels from 40 up to 400 mg/day for several (3-12) weeks do not report adverse effects, except for one study conducting an open trial at a dose level of 40 mg benfotiamine (dosed together with 90 mg pyridoxine hydrochloride and 250 µg cyanocobalamin for 12 weeks) and reporting nausea, dizziness, stomach ache and weight gain at the twelfth week of the study in 8.4% of the patients. Benfotiamine is converted to thiamine, but given the facts that: •benfotiamine is not endogenous in humans, •the bioavailability of thiamine from benfotiamine is higher than that of other sources of thiamine, •benfotiamine in its dephosphorylated form is absorbed and bioavailable, •no toxicological studies have been provided for benfotiamine to evaluate reproductive and developmental toxicity, genotoxicity or long term toxicity of benfotiamine, and •the animal and clinical studies referred to, which were without adverse effects, were not designed to study possible adverse effects of benfotiamine, the Panel concludes that the submitted data are insufficient to demonstrate the safety of the proposed use and use levels of benfotiamine.