Dr. Lonsdale's Letter: Benfotiamine and Allithiamine Should Be Differentiated
I read with attention Dr. Derrick Lonsdale's letter taking exception
to certain statements made in recent advertisements for AOR's pharmaceutical-grade
Benfotiamine supplements. While Dr. Lonsdale deserves our respect for his many
years of advocacy of the benefits of the allithiamines and of tetrahydrofurfuryl
disulfide in particular, we cannot agree with his objections, which range from
mere terminological quibbling to statements which are simply scientifically
Dr. Lonsdale's first objection is to the description of benfotiamine
as "an allithiamine." Dr. Lonsdale insists that the term "allithiamine" should
only ever be used to refer to one specific compound: that first crystallized
by Dr. Fujiwara from heated garlic in the middle of the last century. While
it is quite correct to note that the term originally referred to this particular
thiamine derivative, the term has since come to refer to the entire class of
high-bioavailability thiamine derivatives sharing a common set of biochemical
features – a class which includes benfotiamine.
This fact can readily be confirmed in the primary scientific literature. Many
investigators specifically describe benfotiamine as being "an allithiamine." For
instance, in their randomized, double-blind, controlled study demonstrating
the effectiveness of benfotiamine on neurological functioning and symptomology
in diabetic neuropathy, Stracke et al. describe benfotiamine as "an Allithiamine," which
they explicate to be "a lipid-soluble derivative of vitamin B1 with high
bioavailability."1 Loew, in reviewing the pharmacokinetics of various
thiamine derivatives, describes benfotiamine as "an allithiamine," and
discusses the "lipophilic thiamine analogues, the allithiamines (acetiamine,
benfotiamine, or fursultiamine [TTFD])."2 Again, in their pharmacokinetic
study of tissue distribution of thiamine vs. benfotiamine, Hilbig and Rahmann
describe "benfotiamine, CAS 22457-89-2 as a "lipid-soluble allithiamine."3 Ziems
and colleagues, in their recent study on the metabolism of benfotiamine, introduce
their study with the statement that "Lipid-soluble thiamine
derivatives belonging to the allithiamine group were discovered nearly 40 years
ago."4 Among these agents, they include S-benzoylthiamine-O-monophosphae
(BTMP) – i.e., benfotiamine.
From these and other examples readily identified using a simple PubMed database
search,5,6 and which could doubtless be expanded upon with a hand-search
of full-text articles, it is clear that the use of the term "allithiamine" has
evolved in scientific usage beyond Fujiwara's original, eponymous "allithiamine" compound,
to embrace the entire class of these molecules – prominently including
Dr. Lonsdale also appears uncomfortable with the use of the term "benfotiamine" to
denote BTMP, on the basis that it is "obviously a trade name." While
we do use "Benfotiamine" as the name for AOR's specific pharmaceutical-quality
benfotiamine supplements, and while it is the first such supplement to be made
available in North America, "benfotiamine" is certainly not a trade
name: as a perusal of the biomedical literature will clearly show, it is simply
a common, generic shorthand term for the compound itself, used in many studies
Finally, Dr. Lonsdale states that unlike other allithiamines, benfotiamine
is "subject to the same natural transport mechanisms" as conventional
thiamine salts which "makes the absorption of the thiamine moiety into
cells limited," and therefore benfotiamine will "release an intact
thiamine molecule outside the cell [emphasis in original]" rendering
it no more effective than conventional thiamine salts of increasing cell and
tissue thiamine. However, he provides no data to document this belief. Fortunately,
abundant data exist to refute this misapprehension.
Loew2 specifically states that benfotiamine undergoes the very same
process of cellular absorption and reduction as other allithiamines: "Benfotiamine,
an allithiamine, contains an open thiozole ring that is closed by reduction
within the organism producing physiological thiamine…. Allithiamins differ
from water-soluble thiamine derivatives both in their physiochemical properties
and their structure, specifically their open thiazole ring. They are so-called
prodrugs, which are converted to physiologically active thiamine within the
organism by closure of the thiazole ring." The metabolism of benfotiamine
is discussed in greater detail in a later review,7 which describes
the entire process of absorption and disposition of benfotiamine in
is first taken up across the gut mucosa through dose-proportional passive diffusion
and then converted not to thiamine (as Dr. Lonsdale guesses), but to its first
metabolite, S-benzoylthiamine. This metabolite is then transported to the cell,
where it is again taken up across the neuronal membrane by a process of dose-proportional
passive diffusion. Only at this point is S-benzoylthiamine finally subject
to intracellular reduction to biologically active thiamine.7
That benfotiamine is indeed taken up by cells and tissues more avidly than
either thiamine itself or other allithiamines is demonstrated not only by the
many clinical and experimental studies which clearly show the superiority of
benfotiamine to thiamine in correcting diabetic nerve and kidney dysfunction,
but also by direct pharmacokinetic studies documenting its higher accumulation
and retention within cells and tissues after both oral and intravenous administration
(which latter eliminates the confounding factor of absorption in the GI), and
its especially selective incorporation into neural tissue. On these points,
see studies reviewed by Loew2; see also many subsequently-published original
investigations.3,8-12 In the present context, Greb and Bitsch's study12
is of special interest, because it compared benfotiamine to TTFD (which Dr.
Lonsdale appears to favor) and thiamine disulfide. These investigators found
that benfotiamine was more bioavailable and bioactive than the other two supplements,
not only in increasing plasma thiamine levels, but also in raising levels within
red blood cells and in increasing biological activity as assessed by absolute
Finally, Dr. Lonsdale states that "The prosthetic group from BTMP has
not, to my knowledge, been studied" and that this bears on benfotiamine's
ability to assisting in the excretion of heavy metals. In fact, both sides
of this issue have been addressed, both in studies evaluating the metabolism
of benfotiamine itself and of its first metabolite, S-benzoylthiamine,4,13
and in a study directly showing that benfotiamine increases excretion of tissue
I trust that this information satisfactorily addresses Dr. Lonsdale's
questions. Extensive information on benfotiamine is also available on our website
Dr. Traj P.S. Nibber, Director
Advanced Orthomolecular Research
1. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination
in treatment of diabetic polyneuropathy. Exp
Clin Endocrinol Diabetes.
2. Loew D. Pharmacokinetics of thiamine derivatives especially of benfotiamine.
Int J Clin Pharmacol Ther. 1996 Feb;34(2):47-50.
3. Hilbig R, Rahmann H. Comparative autoradiographic investigations
on the tissue distribution of benfotiamine versus thiamine in mice.
Arzneimittelforschung. 1998 May;48(5):461-8.
4. Ziems M, Netzel M, Bitsch I. Biokinetic parameters and metabolism
of S-benzoylthiamine-O-monophosphate. Biofactors. 2000;11(1-2):109-10.
5. Centerwall BS, Criqui MH. Prevention of the Wemicke-Korsokoff syndrome:
a cost-benefit analysis. N Engl J Med. 1978 Aug 10;299(6):285-9.
6. Price J, Theodoros MT. The supplementation of alcoholic beverages
with thiamine – a necessary preventive measure in Queensland?
Aust NZ J Psychiatry. 1979 Dec;13(4):315-20.
7. Loew D. Development and Pharmacokinetics of Benfotiamine In Gries
FA, Federlin K. Benfotiamin in the Therapy
of Polyneuropathy. New York:
Georg Thieme Verlag, 1998; 19-27.
8. Karpov LM, Rozanov Ala, Filippova TO. Characteristic features of
35S-benzoylthiamine monophosphate in albino mice. Vopr
Med Khim. 1986
9. Geyer J, Netzel M, Bitsch I, Frank T, Bitsch R, Kramer K, Hoppe
P. Bioavailability of water- and lipid-soluble thiamin compounds in
broiler chickens. Int J Vitam Nutr Res. 2000 Dec;70(6):311-6.
10. Frank T, Bitsch R, Maiwald J, Stein G. High thiamine diphosphate
concentrations in erythrocytes can be achieved in dialysis patients
by oral administration of benfotiamine. Eur
J Clin Pharmacol. 20 Jun;56(3):251-7.
11. Frank T, Bitsch R, Maiwald J, Stein G. Alteration of thiamine pharmacokinetics
by end-stage renal disease (ESRD). Int J Clin
Pharmacol Ther. 1999
12. Greb A, Bitsch R. Comparative bioavailability of various thiamine
derivatives after oral administration. Int
J Clin Pharmacol Ther. 1998
13. Shindo H, Okamoto K, Totsu J. Transport of organic compounds through
biological membranes. I. Accumulative uptake of S-benzoylthiamine by
human erythrocytes. Chem Pharm Bull (Tokyo). 1967 Mar;15(3):295-302.
14. Yamamoto J, Kaneda Y. Excretion of intracorporeal cadmium with
S-benzoylthiamin monophosphate. Bull Environ
Contam Toxicol. 1995 May;54(5):745-50.