Best Benfotiamine
120 Veggie Caps
Each capsule
contains:
Benfotiamine..........80mg
Excipients: modified
cellulose (veggie cap),
cellulose, silicon dioxide
Suggested
Adult Use: Take two capsules daily.
120 Veggie Caps
Each
capsule contains:
Benfotiamine..........150mg
Excipients:
modified cellulose (veggie cap),
cellulose, silicon
dioxide
Ingredients
Benfotiamine
(S-benzyolthiamine-O-monophosphate) is a synthetic derivative of
thiamin, belonging to the family of compounds known as
"allithiamines." Benfotiamine is fat-soluble and thus more
bioavailable and physiologically active than thiamin.*
Characteristic of the allithiamines is an open thiazole ring
within the chemical structure of these thiamine-related
compounds, making them fat (lipid) soluble. In contrast,
thiamine, which is water soluble, has a closed thiazole ring.
The lipid solubility of benfotiamine, conferred by this open
ring, increases its bioavailablity. Benfotiamine is readily
absorbed at higher doses, in contrast to absorption of
water-soluble thiamin salts, which decreases at higher doses,
due to saturation of absorption sites in the intestines.1 In a
double-blind, cross-over trial, comparing bioavailability of
benfotiamine to that of thiamine in 12 subjects, benfotiamine
caused an average 5-fold greater increase in blood thiamine
levels than thiamin mononitrate, with a concomitant greater
thiamine concentration in erythrocytes (red blood cells).2
Benfotiamine readily passes through intestinal mucosal cells,
where it is converted into physiologically active thiamine.
Benfotiamine inceases blood levels of thiamine pyrophosphate
(TPP), the primary thiamin co-enzyme.3
Benefits
Benfotiamine raises the blood level of thiamine
pyrophosphate (TPP), the biologically active co-enzyme of
thiamine.4
Thiamine and its Co-enzyme, TPP
Thiamine (vitamin
B1) plays an essential part in the metabolism of glucose,
through actions of it co-enzyme TPP (thiamine pyrophosphate).
TPP is formed by the enzymatically-catalyzed addition of two
phosphate groups donated by ATP to thiamine. TPP also goes by
the name "thiamine diphosphate." In the cytoplasm of the cell,
glucose, a 6-carbon sugar, is metabolized to pyruvic acid, which
is converted into acetyl-CoA, otherwise known as "active
acetate." Acetyl CoA enters the mitochondrion, where it serves
as the starting substrate in the Kreb’s cycle (citric acid
cycle). The Krebs cycle is the primary source of cellular
metabolic energy. TPP, along with other co-enzymes, is essential
for the removal of CO2 from pyruvic acid, which in turn is a key
step in the conversion of pyruvic acid to acetyl CoA. CO2
removal from pyruvic acid is called "oxidative decarboxylation,"
and for this reason, TPP was originally referred to as
"cocarboxylase." TPP is thus vital to the cell’s energy
supply.
Benfotiamine helps maintain healthy cells in the
presence of blood glucose.
Acting as a biochemical
"super-thiamin," it does this through several different cellular
mechanisms, as discussed below.
Benfotiamine and Glucose
Metabolism
Benfotiamine normalizes cellular processes fueled by
glucose metabolites.
As long as glucose remains at normal
levels, excess glucose metabolites do not accumulate within the
cell. The bulk of the cell’s glucose supply is converted to
pyruvic acid, which serves as substrate for production of acetyl
CoA, the primary fuel for the Krebs cycle. Of the total amount
of metabolic energy (in
the form of ATP) released from food,
the Krebs cycle generates about 90 percent.5 In the presence of
elevated glucose levels, the electron transport chain, the final
ATP-generating system in the mitochondrion, produces larger than
normal amounts of the oxygen free radical "superoxide." This
excess superoxide inhibits glyceraldehyde phosphate
dehydrogenase (GAPDH), as key enzyme in the conversion of
glucose to pyruvic acid, resulting in an excess of intermediate
metabolites known as "triosephosphates." Increase triosephophate
levels trigger several cellular mechanisms that result in
potential damage to vascular tissue. Cells particularly
vulnerable to this biochemical dysfunction are found in the
retina, kidneys and nerves.
Benfotiamine has been shown to
block three of these mechanisms: the hexosamine pathway, the
diaglycerol-protein kinease C pathway and the formation of
Advanced Glycation End-poducts. As discussed below, benfotiamine
does this by activating transketolase, a key thiamin-dependent
enzyme.6
Benfotiamine stimulates tranketolase, a cellular
enzyme essential for maintenance of normal glucose metabolic
pathways.*
Transketolase diverts the excess
fructose-6-phosphate and glyceraldehydes-3-phosphate, (formed by
the inhibition of GAPDH, as mentioned above), into production of
pentose-5-phosphates and erythrose-4-phosphate and away from the
damaging pathways. Benfotiamine activates transketolase activity
in bovine aortic endothelial cells incubated in glucose.6 To
test benfotiamine’s ability to counteract these metabolic
abnormalities caused by elevated blood glucose, studies have
been done in diabetic rats. Benfotiamine increases transketolase
activity in the retinas of diabetic rats, while concomitantly
decreasing hexosamine pathway activity, protein kinase C
activity and AGE formation.6
Benfotiamine and Protein
glycation
Benfotiamine controls formation of Advanced Glycation
End-products (AGEs).
AGEs have an affinity for proteins such as
collagen, the major structural protein in connective tissue.
AGEs are formed through abnormal linkages between proteins and
glucose. This occurs via a non-enzymatic glycosylation reaction
similar to the "browning reaction" that takes place in stored
food.7 At high glucose concentrations, glucose attaches to
lysine, forming a Schiff base, which in turn forms "early
glycosylation products." Once blood glucose levels return to
normal levels, the amount of these early glycosylation products
decreases, and they are not particularly harmful to most tissue
proteins. On long-lived proteins such as collagen, however,
early glycosylation products are chemically rearranged into the
damaging Advanced Glycation End-products.
AGE formation on the
collagen in coronary arteries causes increased vascular
permeability. This vessel "leakiness" allows for abnormal
cross-linking between plasma proteins and other proteins in the
vessel wall, comprising vascular function and potentially
occluding the vessel lumen. A number of other potentially
harmful events may also occur, including production of cytokines
that further increase vascular permeability. Endothelin-1, a
strong vasoconstrictor, is over produced, increasing the
possibility of thrombosis and generation of oxygen free radicals
is stimulated.8
It is vitally important to support normal
glucose metabolic pathways so that formation of AGEs is
minimized. Benfotiamine, in the test tube (in vitro) prevents
AGE formation in endothelial cells cultured in high glucose by
decreasing the glucose metabolites that produce AGEs.9
Endothelial cells make up the membranes that line the inner
walls of organs and blood vessels. In a rat study comparing the
effects of Benfotiamine with water-soluble thiamin, Benfotiamine
inhibited AGE formation in diabetic rats while completely
preventing formation of "glycooxidation products," which are
toxic by products of chronic elevated blood glucose. AGE levels
were not significantly altered by thiamin.10 Benfotiamine also
normalized nerve function in the animals. After three months of
administration, "nerve conduction velocity (NCV)," a measure of
nerve function, was increased by both benfotiamine and thiamin;
at six months, NCV was normalized by benfotiamine, whereas
thiamin produced no further increases in this parameter.
Dysfunctional glucose metabolic pathways leading to AGE
formation occurs in endothelial cells of the kidneys. In a
recent animal study, benfotiamine was administered to rats with
elevated glucose levels. Benfotiamine increased transketolase
activity in the kidney filtration system of these rats, while at
the same time shifting triosephophates into the pentose pathway
and preventing protein leakage.11
Safety
Benfotiamine has
an excellent tolerability profile and can be taken for long
periods without adverse effects.3,12
The statements in this
fact sheet have not been evaluated by the Food and Drug
Administration. This product is not intended to diagnose, treat,
cure or prevent any disease.
Scientific References
1. Bitsch
R, Wolf M, Möller J. Bioavailability assessment of the
lipophilic benfotiamine as compared to a water-soluble thiamin
derivative. Ann Nutr Metab 1991;35(2):292-6.
2. Schreeb KH,
Freudenthaler S, Vormfelde SV, et al. Comparative
bioavailability of two vitamin B1 preparations: benfotiamine and
thiamine mononitrate. Eur J Clin Pharmacol 1997;
52(4):319-20.
3. Loew D. Pharmacokinetics of thiamine
derivatives especially of benfotiamine. Int J Clin Pharmacol
Ther 1996;34(2):47-50.
4. Frank T, Bitsch R, Maiwald J, Stein
G. High thiamine diphosphate concentrations in erythrocytes can
be achieved in dialysis patients by oral administration of
benfontiamine. Eur J Clin Pharmacol. 2000;56(3):251-7.
5. Pike
RL, Brown ML. Nutrition, An Integrated Approach, 3rd Ed. New
York:MacMillan; 1986:467.
6. Hammes H-P, Du X, Edlestein D, et
al. Benfotiamine blocks three major pathways of hyperglycemic
damage and prevents experimental diabetic neuropathy. Nat Med
2003;9(3):294-99.
7. Monnier VM, Kohn RR, Cerami A. Accelerated
age-related browning of human collagen in diabetes mellitus.
Proc Natl Acad Sci 1984;81(2):583-7.
8. Brownlee M. The
pathological implications of protein glycation. Clin Invest Med
1995;18(4):275-81.
9. Pomero F, Molinar Min A, La Selva M, et
al. Benfotiamine is similar to thiamine in correcting
endothelial cell defects induced by high glucose. Acta Diabetol
2001;38(3):135-8.
10. Stracke H, Hammes HP, Werkman D, et al.
Efficacy of benfotiamine versus thiamine on function and
glycation products of peripheral nerves in diabetic rats. Exp
Clin Endocrinol Diabetes 2001;109(6):300-6.
11. Babaei-Jadidi
R, Karachalias N, Ahmed N, et al. Prevention of incipient
diabetic nephropathy by high-dose thiamine and benfotiamine.
Diabetes 2003;52(8):2110-20.
12. Bergfeld R, MatsumaraT, Du X,
Brownlee M. Benfotiamin prevents the consequences of
hyperglycemia induced mitochondrial overproduction of reactive
oxygen specifies and experimental diabetic neuropathy (Abstract)
Diabetologia 2001; 44(Suppl1):A39.
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