see the reply to this letter from the advertiser.
I have to object to the advertisement for Benfotiamine on page 132 of your
June issue, since the statements designed to promote it are inaccurate. I
wish to put the record straight concerning the derivatives of thiamine that
have been extremely well studied in Japan. Very little research has been
reported about these important vitamers in recent years, but with the awakening
of information concerning heavy metal poisoning it becomes important for
us to know about the proper use of thiols in therapy.
First, a little history is necessary. The enzyme known as thiaminase was being
studied in the 1940s by members of the University-based Vitamin B Research
Committee of Japan. As a byproduct of these studies, Fujiwara discovered a
derivative of thiamine that was more active biologically than the original
thiamine. After many years of further research into this phenomenon, they produced
a book in English, published in Tokyo in 1965 and obviously hard to obtain.
The authors were particularly concerned that there was considerable ignorance
in the West about the massive amount of research that surrounds the versatile
therapeutic properties of thiamine and its many derivatives.
The following information is extracted from this book. Fujiwara called the
new byproduct of thiamine by the name of allithiamine to indicate that it was
found in garlic bulbs and other members of the allium plant genus. Subsequently,
it was found that allithiamine was a disulfide derivative of thiamine formed
only when an enzyme within the plant acted on thiamine. This action occurs
when the garlic bulb is crushed or cut and allithiamine is one of the many
thiols that produce some of the diverse therapeutic properties of garlic. The
advertisement refers to Benfotiamine as being a member of a group of allithiamines
and that is simply not true. There is only one allithiamine and that is the
one that occurs naturally in the allium plants as described above. Thiamine
tetrahydrofurfuryl disulfide (TTFD), the synthetic counterpart of allithiamine
is presently sold as Allithiamine. Note the capital A, for this product is
not to be confused with the naturally occurring disulfide in garlic.
Fujiwara and his colleagues then went on to do a vast amount of research
that is detailed in the book referenced at the end of this letter. They went
to synthesize a whole series of thiamine derivatives and performed animal
and human subject studies. Much of this experimental work was performed with
propyl disulfide (TPD), the forerunner of the most modern derivative, TTFD.
Both of these "fat soluble" thiamines have the same biologic properties.
Other molecules, synthesized and studied later, are known as S-acyl-thiamine
derivatives. They included O, S-diacetyl thiamine (DAT), O,S-dibenzoyl thiamine
(DBT) and S-benzoylthiamine monophosphate (BTMP), the last one now known
as Benfotiamine and obviously a trade name.
I would like to quote from a chapter in the book that was written by Fujiwara: "While
S-acyl-thiamine derivatives are readily absorbed from the intestinal canal
at a rate comparable to allithiamine, they are devoid of that marked property
of allithiamine (and its synthetic derivatives), i.e. penetration into blood
cells." Later in the text: “S-acyl-thiamine derivatives are devoid
of the preventive effect against the intoxication of various types which
characterize allithiamine: this difference may be ascribed to the absence
of the S-S bond
in S-acyl-thiamine derivatives."
To enlarge on this, experiments in animals showed that TPD partially protected
mice against experimental cyanide poisoning by stimulating the enzyme rhodanese
that is responsible for converting toxic cyanide ions to non-toxic thiocyanate.
They were also able to show that TPD protected animals from experimentally
administered carbon tetrachloride, to mention but two of the many animal studies
that were performed by this group of investigators.
Generally, they said, allithiamine and its synthetic derivatives are very easily
reducible to thiamine in the presence of cysteine or glutathione, an extremely
important part of their biologic action. On the other hand, S-acyl-thiamine
derivatives resist such a simple reduction. They are first reduced to thiamine
only after they are acted on enzymatically in the liver or kidney. This very
important difference needs further explanation, since it affects their biologic
Both the disulfide and S-acyl-thiamine derivatives are formed by opening
the thiazolium ring of thiamine and attaching a prosthetic group to the sulfur
atom of the thiazolium. The disulfide bond is the key and the S-acyl-thiamine
derivatives are not disulfides. For this reason they cannot be referred to
as "fat soluble." The only reason for calling TPD or TTFD "fat
soluble" is because they enable the passage of thiamine across the lipid
barrier of the cell membrane. In fact, TTFD is water soluble and can be given
intravenously. The disulfide is reduced and the prosthetic group (the tetrahydrofurfuryl
mercaptan) is left outside the cell. The opened thiazolium ring closes in
the cell to become an intact molecule of thiamine. This non-enzymatic transport
enables the import of the thiamine moiety into the cell where it is then
of building up high concentrations of thiamine pyrophosphate and triphosphate,
the active forms of the vitamin. The ordinary water soluble salts of thiamine
rely on a transport system across cell membranes that makes the absorption
of the thiamine moiety into cells limited. It would appear that BTMP is subject
to the same natural transport mechanisms by the release of an intact thiamine
molecule outside the cell.
Lastly, the mercaptan prosthetic group of TTFD has been very well studied,
its sequential enzymatic breakdown known, and it is non-toxic. The prosthetic
group from BTMP has not, to my knowledge, been studied and is an important
part of the biochemical transaction that takes place when the molecule is split
into its two factions. Animal studies have shown that thiamine causes lead
to be excreted via the bile duct and kidney. Since lead is SH-reactive, like
mercury, arsenic and cadmium, it is very probable that it is the SH reactivity
that is linked to this and it obviously needs to be explored in the wake of
the increasing knowledge of the toxicity of these heavy metals. If intracellular
thiamine is required for this effect, then it is apparent that TTFD would be
superior to BTMP or water-soluble salts in any other form.
Derrick Lonsdale, MD
Preventive Medicine Group
24700 Center Ridge Road
Westlake, Ohio 44145 USA
1. Fujiwara M. Absorption, excretion and fate of thiamine and its derivatives
in [the] human body. Chapter in: Shimazono N, Katsura, eds: Beriberi
and Thiamine. 1965, Tokyo, Igaku Shoin Ltd. pp.179-213.