Benfotiamine induces Nrf2

[Rhyothemis]

Here's a study on benfotiamine in a mouse model of Alzheimer's -

Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathyncbi.nlm.nih.gov/pmc/articl...

Abstract

"Impaired glucose metabolism, decreased levels of thiamine and its

phosphate esters, and reduced activity of thiamine-dependent enzymes,

such as pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and

transketolase occur in Alzheimer’s disease (AD). Thiamine deficiency

exacerbates amyloid beta (Aβ) deposition, tau hyperphosphorylation and

oxidative stress. Benfotiamine (BFT) rescued cognitive deficits and

reduced Aβ burden in amyloid precursor protein (APP)/PS1 mice. In this

study, we examined whether BFT confers neuroprotection against tau

phosphorylation and the generation of neurofibrillary tangles (NFTs) in

the P301S mouse model of tauopathy. Chronic dietary treatment with BFT

increased lifespan, improved behavior, reduced glycated tau, decreased

NFTs and prevented death of motor neurons. BFT administration

significantly ameliorated mitochondrial dysfunction and attenuated

oxidative damage and inflammation. We found that BFT and its metabolites

(but not thiamine) trigger the expression of Nrf2/antioxidant response

element (ARE)-dependent genes in mouse brain as well as in wild-type but

not Nrf2-deficient fibroblasts. Active metabolites were more potent in

activating the Nrf2 target genes than the parent molecule BFT. Docking

studies showed that BFT and its metabolites (but not thiamine) bind to

Keap1 with high affinity. These findings demonstrate that BFT activates

the Nrf2/ARE pathway and is a promising therapeutic agent for the

treatment of diseases with tau pathology, such as AD, frontotemporal

dementia and progressive supranuclear palsy."

Excerpt from Discussion

"After oral administration, BFT is hydrolyzed in the intestine into the

lipophilic s-BT that diffuses across the epithelial membranes into the

blood or liver, where it is converted into thiamine (40).

As a result, blood thiamine concentrations reach 5-fold higher levels

and persist longer than after administration of an equivalent dose of

thiamine. Nevertheless, the magnitude of the rate of thiamine uptake

into the brain is limited, in part, by a self-exchange mechanism

catalyzed by the high affinity thiamine transporter (2)."

[SilentEchoes]

Benfotamine and allithiamine are on my list to investigate. Do you know what dose is recommended? Can benfotamine be taken in addition to thiamine hcl?

The Townsend Letter article talks about thiamine to detoxify heavy metals. Hormones Matter talks about Lipothiamine (TTFD). "The Japanese scientists studied the effect of cyanide in mice and found that thiamine propyl disulfide (TPD), a forerunner of TTFD, gave significant protection from the lethal effect of this poison, an incredible discovery that alone should raise eyebrows. "

Could this be why HDT has been so helpful in PD?

townsendletter.com/AugSept2...

hormonesmatter.com/ttfd-thi...

One of the observations I've made is there seems to be impairment of phosphorylation in neurodegenerative disorders. I'm also researching B6 (P5P).

Maybe we need to be taking activated forms of these vitamins.

I don't have enough education or experience to fully understand the biological process. I mainly look for contraindications and try to avoid pharmaceutical drugs.

researchgate.net/publicatio...

sciencedirect.com/science/a...

*FTD is the other end of the spectrum of ALS.

I love this quote from Dr. Lonsdale:

"Thiamine derivatives represent a new basic principle of therapy. It recognizes that healing is a function of the body, not the activity of a so-called “healer”. All it requires is the foundation substances needed for repair and sufficient energy to use them. It demands a dramatic change in thinking about health and disease. If you understand the principles involved, it forces the conclusion that the word “cure” is a pipe dream. The only form of pharmaceutical drug that matters is one that safely kills an attacking microbe. Almost all the rest of them merely relieve symptoms and have no effect on the ultimate outcome."

SE