Mega-Dose Thiamine: Benefits Beyond Addressing Deficiency

[Music] hi this is elliot from eo nutrition and in today's video we will be examining the rationale

behind using megadoses or extremely high doses of a nutrient called thymine or vitamin b1 so this particular vitamin has been used in human clinical trials

for a wide variety of different health conditions and it is been shown to in some people at least produce major symptomatic approval now why i've seen this on

numerous occasions uh in my own clinical practice with the people that i work with and again i would like to try to explain that in this video how that is working because i do not

think it is simply acting to replete nutritional status or address a deficiency in fact simply addressing a deficiency is not

going to help it's not going to explain the the magnitude of effects that are seen when very high doses are used you know in contrast pharmacological doses i

think are having an effect on cellular energy metabolism restoring energy metabolism when it has been disrupted or inhibited by other factors

so to quickly summarize in very simple terms there are lots of things which can disrupt how cells make energy and when cells lack energy they cannot work efficiently

so the idea behind or the rationale behind using megadoses of b1 is that it has a particular capacity to stimulate certain enzymes involved in energy

metabolism and restore metabolic function in cells so that they can begin working as they previously did and so this is the kind of thing that i see in clinical practice this

has has been noted in the scientific research we will go through that at the end of this video we will also look at the potential mechanisms with regard to how this works

so hopefully by the end of the video you will have a much better understanding as to why high doses or megadoses of thymine are sometimes necessary to achieve certain effects which cannot be gotten

through dietary levels so first of all to summarize here are the key points high dose thymine has been used to improve the symptoms in a wide variety

of different health conditions i think one of the ways that this works is because thymid dependent enzymes

can be selectively disrupted by toxins by chronic oxidative stress and inflammation now what this does is it produces this same

scenario the same biochemical situation as having a deficiency but this is not a dietary deficiency this is a functional deficiency

now ordinary levels from the diet are not sufficient to overcome the inactivation of these enzymes in fact pharmacologic doses so extremely

high doses can and do restore enzyme activity so by saturating these enzymes

with the cofactor with thymine you can effectively restore normal energy metabolism and because of this someone does not necessarily need to be

deficient in the dietary sense to benefit from this type of therapy now briefly we will need to go through the very basics of enzymes

this is just a quick run through just so that you can understand the principles and i go into this in a little bit more depth in the article which has been linked in the show notes but basically

what you have to understand i've spoken about this in previous videos is that nutrients many times they act as co-factors for enzymes in the human body that's how we use them that's how they are

necessary and so enzymes are types of proteins which are responsible for speeding up biochemical reactions many enzymes they help convert one thing into another thing

or they help build things or help break things down that's all that you need to know now enzymes oftentimes they need cofactors or coenzymes and it's basically the same

thing and the coin factor when it is bound with the enzyme it can effectively allow the enzyme to do its job so in this context

it's converting a to b now enzymes have an affinity for their specific cofactor okay so when the cofactor affinity

is high that means it binds very tightly with the cofactor and the this binding increases the rate of the enzyme function or increases the rate of reaction

now on the other hand if an enzyme has a lower coenzyme binding affinity lower ability to bind with its cofactor then we get a reduced

enzymatic function or a reduced rate of reaction so why is this important well what you need to know is that there are a variety of

genetic conditions which are inherited and what this basically means or something that is present in these conditions listed on the screen

is that the people with these genetic conditions the way that they make proteins the way that they make specific enzymes is slightly different to the average person

and that would depend on the gene that has the defect so i'll give you an example in a condition which is called b1 responsive maple syrup urine disease

these people have a defect in a gene which allows them to make a protein called branched chain ketoacid dehydrogenase it's a very long long name but essentially what you need to know

is it's an enzyme and it helps us break down branched-chain amino acids and this enzyme ordinarily uses thymine okay uses thymine as a cofactor

but in this genetic defect the enzyme that they make has very low affinity for thymine as a cofactor and what that means is that the ordinary amounts that they get from the diet are not

sufficient to drive the function of this enzyme this means that these people can end up with severe metabolic dysfunction and in some cases

they might die very early on now the way that this particular variant has been treated medically is by using very high doses of thymine it's the same as the rest of

these conditions and many other conditions there are and there's another condition called b1 responsive lase disease and this involves a defect in um the gene which

encodes pyruvate dehydrogenase another enzyme which uses thiamin on the other hand we have a condition

called methylmelonic acidemia and this again is a defect in encoding for an enzyme which uses b12 there's another one called b6 responsive

homocysteine urea now all of these conditions what they have in common is that they can be treated medically by giving

very high doses of the nutrient cofactor specific for the enzyme which is not being made correctly how does this work well in very simple terms

we spoke about how enzymes have affinity for their cofactor and if someone is making enzymes with very low affinity it means that it's only going to be able to bind

a very small amount of the cofactor it's going to be equivalent to this person being severely deficient in the nutrient despite how much they get through the diet now

if we look at how nutrients can be used by giving extremely high doses of the nutrients in other words by saturating the enzymes

we can overcome the lack of affinity by giving mega doses of these nutrients this lack of affinity can be

overcome we can bypass this defect by saturating cells or saturating enzymes with enough of the cofactor so that it

can start working as it ordinarily should do so the large majority of people do not

have these genetic conditions however we can use very similar principles and apply them to chronic diseases now the reason for this is is because

it's not just genetics which can affect whether an enzyme runs or works as it should do or not in fact many of the energy or many of the

enzymes which are involved in energy metabolism can be inhibited or activated via various factors if we look at many of the enzymes they are

naturally inactivated or naturally inhibited as part of normal human physiology right we need to turn on enzymes at different times and turn them off

based on metabolic demand there are many other factors which can inhibit our enzymes the enzymes which we use to generate energy in the cells they can be

inhibited and when this goes on for long enough in a specific way then this can become pathological what this means is is that this can contribute

to disease processes one specific specific type of enzyme is called alpha-ketoglutarate dehydrogenase this requires multiple nutrients

to function one of those nutrients is thymine thymine is a cofactor for this enzyme complex now this particular enzyme is what is referred to as a rate limiting enzyme

it's a rate limiting step in a cycle which is called the tca cycle or the krebs cycle now what rate limiting essentially means is that when this enzyme

slows down in activity every other step after it in energy metabolism is also going to be slowing down now this can be beneficial in certain circumstances

but it can also be potentially detrimental when this goes on unnaturally that's important to know that this enzyme is uniquely sensitive to inactivation

by oxidative stress now this has been identified to be inactivated or inhibited in multiple chronic diseases and it's been said by various researchers that under chronic

conditions when this enzyme is chronically inactivated it likely contributes towards pathology

so heavy metals excitotoxic chemicals oxidized products of neurotransmitters and neuroinflammatory products all have an inhibitory effect on this enzyme

and likely contribute towards disrupted energy metabolism and this is going to be found particularly in the brain

now what can lead to the production of excess amounts of these chemicals well we see that there are lots of things that are involved in

toxicity or lots of things which can have neural inflammation as a component so exposure to biotoxins this can be mycotoxins this can be other types of

toxins produced by lyme disease for instance this can modulate the immune system in the brain to activate the inflammatory response we see emf radiation

so electromagnetic frequencies mobile phone radiation wi-fi etc these can trigger the excitotoxic cascades which increase peroxide nitrate in the brain

increase nitric oxide chronic infection chemical toxins heavy metals again these things are ubiquitous in the environment all of these things can contribute

towards an inhibitory effect on this enzyme system when there is chronic oxidative stress when there is chronic inflammation particularly

neuroinflammation we see that this enzyme is inhibited several of these chemicals also have an inhibitory effect on the pyruvate dehydrogenase complex

which once again is also dependent on thymine as a cofactor so two key energy producing enzymes or enzymes involved in

energy metabolism both requiring thymine are both inhibited by a variety of factors which are not related to a deficiency

and so how does this relate to the topic of this discussion how does this relate to mega dosing of thymine well a very interesting research paper came out

in 2018 it was called thymine preserves mitochondrial function in rap model of traumatic brain injury preventing in inactivation of ketoglutarate

dehydrogenase complex and so in this study they showed that rats who had been exposed to traumatic brain injury and what they found was that

there was lots of oxidative stress and what this did was it inactivated the alpha-ketoglutarate dehydrogenase complex it reduced atp synthesis and there was lots of neuro inflammation as

well so basically the damage caused by traumatic brain injury affected how the cells made energy they made a lot less energy now what they also did was they exposed

another group of rats to a similar head trauma but before that experiment what they did was they pre-treated them they gave them extremely high doses of

thymine pre-trauma and what they found was that the rats that had very high doses of thymine they found that there was no inhibition

of the alpha-ketoglutarate dehydrogenase enzyme in fact it remained exactly the same they also found that mitochondrial function was um

was protected they did not find a reduction of atp in fact the cells maintained energy production like they would have if they did not

have a traumatic brain injury they also found some indicators of reduced neuroinflammation and so what they concluded was that mega

doses of thymine protected against the effects of this insult and this was outside the context of a

deficiency these rats were not deficient per se but the trauma produced a situation which was very similar to deficiency and by giving very high doses they could

overcome or they could bypass that inactivation and so what do we see we see that this is evidence of how multiple different factors

multiple different influences whether it be any of those things at the top of this diagram which can produce oxidative stress which can produce chronic inflammation

these things will inhibit enzymes the enzyme which is most susceptible to these effects is alpha-ketoglutarate dehydrogenase and it turns out

that that requires thymine to work so we use a similar principle giving very high doses saturating the enzyme with the nutrient and what we find is is that that can

bypass this inactivation so giving very high doses of thymine beforehand prevented the inactivation of this enzyme and maintained

energy metabolism as it was prior another study was also looking at traumatic brain injury there are measuring levels of glutamate which is involved in neuroexcitotoxicity it's one of the excitatory

neurotransmitters what they found was that the rats who had been exposed to traumatic brain injury um their brain had been injured they had got massive amounts of glutamate in the brain

which was causing this excitotoxic cell death now what they found was that very high doses of thymine before trauma pre-trauma increased glutamate clearance in the brain

and also protected the cells against cell death once again this was outside of the context of deficiency these rats were not deficient in thymine

before the experiment so this is demonstrating that thymine has a certain medicinal quality protecting the cells by preventing the

inactivation of enzymes caused by other factors another study was looking at neuroinflammation which was caused by radiation exposure now what they found

was that high doses of thymine before the exposure reduced inflammation and increased lifespan significantly another model of spinal cord injury

showed greater clearance of nitric oxide maintained levels of brain glutathione which was highly protective in this condition

in oxidative stress megadoses have been shown on numerous occasions to reduce markers of vascular endothelial oxidative stress the authors of one study concluded the

impairment of the alpha-ketoglutarate dehydrogenase enzyme plays a key role in glutamate media mediated neuro excitotoxicity

in neurons during traumatic brain injury so in other words it is the um the inactivation of this enzyme which is responsible for some of the

cell death that occurs in injury now here they go on to say pharmacological activation meaning very high doses of the nutrient

cofactor using a similar principle as we've discussed previously pharmaco pharmacological activation of this enzyme may thus be of

neuroprotective potential this has also been shown in relation to another one of the thymum independent enzymes we're looking at one called transketolase transketolase

is involved in a biochemical pathway called the pentose phosphate pathway and this is involved in recycling glutathione there is research showing that giving

mega doses of thymine what this does is it increases the expression of this enzyme and it increases the activity of this enzyme and this is theoretically one of the

reasons why megadoses of thymine can help to maintain glutathione levels even in the event of a severe stressor which is

known to deplete glutathione a similar principle also applies to an enzyme which we discussed previously pyruvate dehydrogenase

this is using thymine as a cofactor once again there are multiple factors which have been shown to inhibit this this enzyme now this is ordinarily inhibited in a thymic

deficiency however these factors are separate to a deficiency we're not talking about deficiency we're looking at oxidative stress for instance

copper toxicity cardiac ischemia by saturating the enzyme with the cofactor you can overcome that inhibition you can bypass that inhibition

and so high doses of thymine have been shown to reactivate the enzyme now if you want the details of this stud these studies once again these are on my website they are

linked in the show notes so just to summarize we have this principle of enzyme inactivation we have this principle of using high

doses of a nutrient cofactor to stimulate enzyme activity even when it's like even when it's been inactivated this has been demonstrated mechanistically but

in the human research this is where it really shines there was a doctor a late neurologist based in italy his name was constantini now he did studies using

extremely high doses of thymine hydrochloride and he published his results in several journals just a brief overview of some of the effects

or some of the results he got using megadoses of thymine he studied um the effects of thymine in fibromyalgia in many of the the symptoms included in

the depression including the fatigue and he found abrupt and immediate improvement and this was between 1 500

and 1 800 milligrams per day in multiple sclerosis or significant improvements in neurological symptoms at similarly high doses in parkinson's

one of the studies showed between 30 and 70 percent improvement and some of the symptoms some of the patients with a more mild form of the condition

went into complete clinical remission as long as they remained on very high doses of b1 other conditions studied include dystonia friedrich

ataxia the fatigue associated with inflammatory bowel diseases and essential tremors now the question is were all of these people deficient

were all of them dietary deficient in the ordinary sense and is this why they got such an immense benefit from taking thymine in such high doses

well i would say that that's probably not the case now to quote constantini here he said in one of his research papers from this clinical observation it is reasonable to infer

that to thymine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centers that are typically affected by this disease

i think he was talking about parkinson's in that particular study now note that he said a deficiency due to enzymatic abnormalities

so these people probably getting enough in the diet now this is very similar to what i've been speaking about this concept of a functional deficiency this concept of someone

having the enzymes involved in energy metabolism inhibited they're inactivated by other things and this produces a very similar

situation to being dietarily deficient but the amounts that you can get from the diet are not sufficient to overcome this inactivation here is another quote we may suppose that symptoms decrease when the

energetic metabolism and other thyme independent processes return to physiologic levels so basically saying that by giving

very high doses you are returning thyme independent processes back to normal you are restoring whatever deficit was there however they say our aim was not

to correct a systemic deficit of thymine but rather to increase the activity of enzymes involved in cell production of energy

in selective brain regions here we go so this is exactly the kind of concept i'm trying to explain is that we're not looking at addressing a deficiency but rather

we are correcting the activity or stimulating the activity of specific enzymes thyme independent enzymes this being pyruvate dehydrogenase

this being potentially transketolase but this certainly most certainly being alpha ketoglutarate dehydrogenase by giving very high doses we can restore

normal energy metabolism even when those enzymes have been inactivated by the factors which we've previously discussed this means oxidative stress this means

toxins this means inflammation okay some other reasons why thiamin might

also be achieving a benefit at such high doses is that when it's given it exhibits anti-stress properties here are

some of the things which have been found in multiple research studies on a form of thymine called benfotimin showing that this nutrient can be highly

anti-inflammatory it can reduce markers of oxidative stress in the cells and act in an antioxidant fashion it's important to note that in some of these studies done by

constantini benefits were not seen at lower doses in fact in fibromyalgia two of the two of the subjects only saw benefit once they

reached 1500 milligram and they only saw significant benefit when they reached 1800 milligram i described this as an all or nothing effect in that

doses anywhere below that had basically no symptomatic improvement whereas only when they reached a certain threshold that they saw great improvements

to summarize high doses of thymine can be used to overcome metabolic blocks these metabolic blocks can be caused by

a variety of different problems which are not related to a deficiency in the first place this can be traumatic brain injury this can be neuroinflammation this can be chronic

oxidative stress this can be heavy metal poisoning this could be any number of different things okay and these physiological conditions

the neuroinflammatory processes the chemical toxins the oxidative stress these are present in a wide variety of different health conditions this can

be chronic fatigue syndrome it can be adhd it could be fibromyalgia it could be any number of different conditions feature some degree of these kind of processes taking place

and it's theoretically possible that one of the reasons why thymine can benefit so many people in in when it's used in high doses and this is something that i can

corroborate clinically that i see clinically and i want to understand i think one of the reasons why this works is because

it's having a stimulating effects on enzymes which have been blocked and thymine when it's used to sufficiently saturate cells you can help to overcome that

block you can help to restore normality or you can help to normalize how cells can make energy and allow them to return to a place where they can

function as they need to function i've seen people from all walks of life benefit from this particular nutrient when given in a high dose

and i don't believe that they are classically deficient or even insufficient in the dietary sense to benefit from this in fact these people oftentimes

they follow a really clean diet they have done lots of work on their digestion they've done lots of work on their gut health they've done lots of work on trying to optimize their nutrition

and it's only when we get up to the 500 times rda or 1 000 times the rda that they see major improvements and this is exactly what dr constantini demonstrated in his in

his research studies what it seems to be doing is it's either acting on some kind of a genetic level to increase expression or production of of enzymes

of energy metabolism or it's simply saturating enzymes that have been inactivated and restoring some kind of function if you like this video and you found it

helpful please like and subscribe you can find me on facebook as eo nutrition subscribe to my youtube page you can find my website at www.eonnutrition

www.eonnutrition um and i will be making more videos like this in the future you can see the full reference article on my website which is linked in the

show description so until then i'll see you next time