Milgamma
(cyancobalaminum + benfotiaminum)
Bibliography and References. Review.
List of selected scientific articles (abstracts). Experimental and clinical data.
|
 |
|
| Milgamma tablets consist of two active ingredients, benfothiamine and cyancobalamine. They are prescribed in the early stages of diabetic neuropathy to prevent the development of the disease. Even though diabetes is the original illness the medicine was prescribed for, it can be used in the treatment of various neurological disorders, such as polyneuropathies, neuralgia, herpes, facial paralysis, rheumatism and heart problems. All of these are caused to a certain degree by Vitamin B deficit in the body, and thus administering this vitamin along with Milgamma is essential to successful treatment.
Int J Clin Pharmacol Ther. 2005 Feb;43(2):71-7. OBJECTIVE: The aim of the study was to evaluate the efficacy of benfotiamine
administered over three weeks (allithiamine; a lipid-soluble vitamin B1
prodrug with high bioavailability) to patients with diabetic polyneuropathy
in a randomized, placebo-controlled, double-blind, two-center pilot study.
MATERIAL AND METHODS: Forty inpatients (23 male, 18 female, age range
18 - 70 years) with a history of type 1 or 2 diabetes and polyneuropathy
of not longer than two years, were included in the study. Twenty Patients
received two 50 mg benfotiamine tablets four times daily and 20 patients
received placebo over the three-week study period. Two clinical units
were involved with 10 patients receiving placebo and 10 patients benfotiamine
in each. The neuropathy score according to Katzenwadel et al. [1987] was
used to evaluate symptoms of polyneuropathy, vibration perception threshold
and both the physician's and the patient's own assessment were documented.
RESULTS: A statistically significant (p = 0.0287) improvement in the neuropathy
score was observed in the group given active drug when compared to the
placebo-treated controls. There was no statistically significant change
observed in the tuning fork test. The most pronounced effect on complaints
was a decrease in pain (p = 0.0414). More patients in the benfotiamine-treated
group than in the placebo group considered their clinical condition to
have improved (p = 0.052). No side effects attributable to benfotiamine
were observed. The differences between the groups cannot be attributed
to a change in metabolic parameters since there were no significant alterations
in the HbA1 levels and blood sugar profiles. The body mass index of the
two groups did not differ. CONCLUSION: This pilot investigation (BEDIP
Study) has confirmed the results of two earlier randomized controlled
trials and has provided further evidence for the beneficial effects of
benfotiamine in patients with diabetic neuropathy. Diabetes Metab Res Rev. 2004 Jul-Aug;20(4):330-6. BACKGROUND: High glucose induces pathological alterations in small and
large vessels, possibly through increased formation of AGE, activation
of aldose reductase and protein kinase C, and increased flux through the
hexosamine pathway. We showed previously that thiamine and benfotiamine
correct delayed replication and increase lactate production in endothelial
cells subjected to high glucose. We now aim at verifying the effects of
thiamine and benfotiamine on cell cycle, apoptosis, and expression of
adhesion molecules in endothelial cells and pericytes, under high ambient
glucose. METHODS: Human umbilical vein endothelial cells and bovine retinal
pericytes were cultured in normal (5.6 mmol/L) or high (28 mmol/L) glucose,
with or without thiamine or benfotiamine, 50 or 100 micro mol/L. Apoptosis
was determined by two separate ELISA methods, measuring DNA fragmentation
and caspase-3 activity, respectively. Cell cycle and integrin subunits
alpha3, alpha5, and beta1 concentration were measured by flow cytometry.
RESULTS: Apoptosis was increased in high glucose after 3 days of culture,
both in endothelium and pericytes. Thiamine and benfotiamine reversed
such effects. Neither cell cycle traversal nor integrin concentrations
were modified in these experimental conditions. CONCLUSIONS: Thiamine
and benfotiamine correct increased apoptosis due to high glucose in cultured
vascular cells. Further elucidations of the mechanisms through which they
work could help set the basis for clinical use of this vitamin in the
prevention and/or treatment of diabetic microangiopathy. Copyright 2004
John Wiley & Sons, Ltd. Diabetes. 2003 Aug;52(8):2110-20. Accumulation of triosephosphates arising from high cytosolic glucose
concentrations in hyperglycemia is the trigger for biochemical dysfunction
leading to the development of diabetic nephropathy-a common complication
of diabetes associated with a high risk of cardiovascular disease and
mortality. Here we report that stimulation of the reductive pentosephosphate
pathway by high-dose therapy with thiamine and the thiamine monophosphate
derivative benfotiamine countered the accumulation of triosephosphates
in experimental diabetes and inhibited the development of incipient nephropathy.
High-dose thiamine and benfotiamine therapy increased transketolase expression
in renal glomeruli, increased the conversion of triosephosphates to ribose-5-phosphate,
and strongly inhibited the development of microalbuminuria. This was associated
with decreased activation of protein kinase C and decreased protein glycation
and oxidative stress-three major pathways of biochemical dysfunction in
hyperglycemia. Benfotiamine also inhibited diabetes-induced hyperfiltration.
This was achieved without change in elevated plasma glucose concentration
and glycated hemoglobin in the diabetic state. High-dose thiamine and
benfotiamine therapy is a potential novel strategy for the prevention
of clinical diabetic nephropathy. Nat Med. 2003 Mar;9(3):294-9. Epub 2003 Feb 18. Three of the major biochemical pathways implicated in the pathogenesis
of hyperglycemia induced vascular damage (the hexosamine pathway, the
advanced glycation end product (AGE) formation pathway and the diacylglycerol
(DAG)-protein kinase C (PKC) pathway) are activated by increased availability
of the glycolytic metabolites glyceraldehyde-3-phosphate and fructose-6-phosphate.
We have discovered that the lipid-soluble thiamine derivative benfotiamine
can inhibit these three pathways, as well as hyperglycemia-associated
NF-kappaB activation, by activating the pentose phosphate pathway enzyme
transketolase, which converts glyceraldehyde-3-phosphate and fructose-6-phosphate
into pentose-5-phosphates and other sugars. In retinas of diabetic animals,
benfotiamine treatment inhibited these three pathways and NF-kappaB activation
by activating transketolase, and also prevented experimental diabetic
retinopathy. The ability of benfotiamine to inhibit three major pathways
simultaneously might be clinically useful in preventing the development
and progression of diabetic complications. Acta Diabetol. 2001;38(3):135-8. We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation. Zh Nevrol Psikhiatr Im S S Korsakova. 2001;101(12):32-6. Benfogamma efficacy in alcoholic polyneuropathy therapy with pain syndrome
and other sensor disorders has been studied. Fourteen males with stage
II-III chronic alcoholism (mean age 41.2 +/- 9 years, mean alcoholism
duration 20.6 +/- 6 years, mean alcoholic polyneuropathy therapy duration
6.8 +/- 4.9 years) have been examined, 93% of the cases having positive
family history of alcoholism. Clinical neurophysiological examination
was conducted at the beginning and at the end of 6-week therapy, 450 mg/day
(2 weeks) and 300 mg/day (4 weeks). During the treatment the regress of
algic, other sensor and movement disorders, as well as some neuropathy
symptoms has been observed. The evidence of positive dynamics at peripheral
and segmental nerve system level was supported by neurophysiological data. FArzneimittelforschung. 1999 Mar;49(3):220-4. The therapeutic effectiveness of a benfotiamine (CAS 22457-89-2)-vitamin B combination (Milgamma-N), administered in high (4 x 2 capsules/day, = 320 mg benfotiamine/day) and medium doses (3 x 1 capsules/day), was compared to a monotherapy with benfotiamine (Benfogamma) (3 x 1 tablets/day, = 150 mg benfotiamine/day) in diabetic patients suffering from painful peripheral diabetic neuropathy (DNP). In a 6-week open clinical trial, 36 patients (aged 40 to 70 yrs) having acceptable metabolic control (HbA1c < 8.0%) were randomly assigned to three groups, each of them comprising 12 participants. Neuropathy was assessed by five parameters: the pain sensation (evaluated by a modified analogue visual scale), the vibration sensation (measured with a tuning fork using the Riedel-Seyfert method) and the current perception threshold (CPT) on the peroneal nerve at 3 frequencies: 5, 250 and 2000 Hz). Parameters were registered at the beginning of the study and at the end of the 3rd and 6th week of therapy. An overall bneneficial therapeutic effect on the neuropathy status was observed in all three groups during the study, and a significant improvement in most of the parameters studied appeared already at the 3rd week of therapy (p < 0.01). The greatest change occurred in the group of patients receiving the high dose of benfotiamine (p < 0.01 and 0.05, resp., compared to the othr groups). Metabolic control did not change over the study. It is concluded that benfotiamine is most effective in large doses, although even in smaller daily dosages, either in combination or in monotherapy, it is effective.
Folia Med (Plovdiv). 1997;39(4):5-10 |
|
|
|
|
