Thiamine (Vitamin B1) Discussion

This is some random article on thiamine, and I don't even know the source:

http://education.med.nyu.edu/courses/advancedscisel/toxicology/courseware/Class1/GRBQ086-C75A-22%5B1162-1166%5D.pdf

But the author cites a lot of articles, and the author discusses a dosage range of 100-200 mg/d as being the range that would tend to produce maximal effects. I just don't think the 500 mg-1,000 mg/d dosage range (and there are studies in people with Alzheimer's using up to 8,000 mg/d) is rational. It's not likely to be toxic per se, but that's not the issue. The issue is the whole competition for transport type of thing (discussed in my last posting).

Even though these are extreme cases, there is a rationale for using that type of "pharmacological" dosage range of 100-200 mg/d (that's not a high dose, as studies go, and there are countless articles talking about dosages bizarrely-higher than those) for mitochondrial damage or impairments from "generic" or nonspecific causes (from mechanisms that wouldn't specifically or selectively affect the thiamine-derived-cofactor-dependent enzyme systems). This type of article, in which researchers used thiamine to treat lactic acidosis that had developed in people taking antiretrovirals, is an example: (http://www.ncbi.nlm.nih.gov/pubmed/10583359). I think all the research on the use of uridine to treat mitochondrial impairment is more promising. Lactic acidosis is life-threatening in a person with HIV, and anyone experiencing any problems with antiretrovirals should talk to his or her doctor, obviously.

But the idea that the thiamine-dependent enzyme systems are saturated at intakes of 1 or 2 mg/d of thiamine is not true. It's not consistent with hundreds of articles, some of which that author cited in the first article. I don't know what dosage would produce saturation, but a lot of the concepts of saturation and so forth can be irrelevant in a lot of contexts. There can be really major intestinal absorption issues in liver disease, but there could also be oxidative inactivation of thiamine cofactors, etc., etc. Who knows.

At the same time, things like thiamine can sometimes produce these limited, transient benefits that sort of wither away, like in some of the articles in the context of neurodegeneration. Thiamine is more of an adjunct, but there's a lot of new research showing that it can protect against complications from diabetes in animal models. I should look at some of the animal dosage ranges, for my own enlightenment. But the use of thiamine seems to me to be a more conservative approach, as opposed to the use of the lipid-soluble prodrugs of thiamine (benfotiamine, etc.), particularly in the absence of diabetes. This article actually shows that thiamine was effective in improving lipid metabolism, in the liver in animals, but benfotiamine wasn't: (http://www.ncbi.nlm.nih.gov/pubmed/15662560). The 70 mg/kg bw dose of thiamine, in most of those newer animal studies in rats, scales to about 15 mg/kg bw for a human (1,050 mg/d for a 70-kg human). That's likely to be a pretty excessively-large dose, and it's being given to diabetic rats, anyway. Maybe there are articles showing long-term benefits from those kinds of doses in humans, but I think there are really diminishing returns as the dose is increased above the 100-200 mg/d, or even 50 mg/d, range. It can be really hard to interpret the effects over the long term, at higher doses. Who's to say the effect isn't the result of some crazy interaction with reduced folates or biotin or something (see references in previous posting).