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Pyruvate dehydrogenase function depends on thiamine (B1)

Chocolove

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@Skippa @JasonUT
This thread seems to be our attempt at figuring it out and everyone is unique. It seems many of us are experimenting with some combination of lipid soluble Thiamine (aka allithiamine, lipothiamine, benfotiamine, fursultiamine and/or sulbutiamine). Quality B-complex, Multi, Magnesium, other electrolytes, and nutrients may be needed to avoid refeeding syndrome. This thread is a good read with a lot of very smart people contributing. It's worth a read when you have time and energy.
It is not just about the dangers of refeeding syndrome.

It is also about what is required for our body's enzymes to even work. Think of your body as a factory full of various machine systems. In order to start the machines usually two or more keys are needed to start with. You can look up enzyme database research to see which enzymes require what factors and co-factors to be utilized. Without all the required factors, it simply won't work. (Words that end in -ase are frequently enzymes.)

Pyruvalte dehydrogenase is an important enzyme in a system that generates energy in many body systems and at the base cellular level. (Fatigue anyone?) This particular enzyme needs thiamine and magnesium to function. Many people have magnesium deficient diets and thiamine deficiencies caused by various things, which should be removed to prevent excretion (such as alcohol...) Without magnesium onboard, you can add all the thiamine in various forms that you like and the enzyme simply won't work.

If you look up common nutrient deficiencies you will find that magnesium is very often deficient in the population at large and many enzymes require it, thus this may be a key to many chronic diseases.

It's about restoring your levels of required nutrients in order to function. First you need to figure out where you might be deficient and why. Fix those problems that are causing nutrient loss and find a source of the nutrients that your body can utilize in a safe way.

Active forms of vitamins can be dangerous in too large amounts because it sends the rickety machinery into overdrive and crash. Sometimes very little can send a person into crash. (For example, Methylfolate is famous in these forums for putting people on the floor wondering if they will survive.) Thiamine and it's derivatives appear to be less dangerous...but again the energy given might stress out another weak part of the body?

Infections require a lot of work by the body to fight and thus the body may end up needing more nutrients. While the body is an amazing healing machine, it cannot work without required nutrients. Some of us may have needs for particular types or forms of nutrients that others don't require.

If you have a normal healthy digestive system consuming nutrients through good healthy food is wonderful. The gut is absolutely amazing in that it will try to protect you from too much of something - our bowels will loosen or totally and violently flush. Think of milk of magnesia: too much of magnesium at once causes the bowels to loosen and so it is sold to do that.

We must always remember that consumption does not equal absorption -even with supplements. If your gut is failing or perturbed, you may not absorb nutrients either in foods or in oral supplements, and might need to consider sub-lingual (under the tongue) or transdermal (through the skin by lotion) application as absorption techniques. IVs are another approach but can stress out the body when too much or too little of the right or wrong stuff is given. Once it's in the body it may be difficult to get rid of. These methods bypass the safety systems of the gut to dump out what you shouldn't have at the moment or what may be dangerous, like a pathogen.

Unfortunately once a nutrient deficiency gets massive and critical, it is hard to replete without some form of supplementation. Finding out what one needs can be a marathon. It's not just about energy. We've all probably tried caffeine till the body malfunctioned. It needs what it needs. Wish it would tell me in English but instead it just keeps cursing me with a myriad forms of malaise and pain as it shuts me down.
 
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@Chocolove nice write-up, thanks for taking the time.

All the supplements I ever try (think I've got an open bottle of thiamine and maybe b complex around) give "undesirable" effects, even if they also seem to help.

I'll keep an eye on this thread for the optimum combo. Ps, i can't handle supplemental magnesium either, get the heeby jeebies.
 

Sidereal

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I am enclosing a thorough review on what was known about thiamine experiments in 2009. It includes issues like magnesium role in pyruvate dehydrogenase activation, serotonin uptake (transient improvement with SSRIs - better addressed in the 2nd chapter linked below), brain lactate, ER stress, accumulation of pyruvate intermediates, etc.
Very interesting paper, thanks @Gondwanaland. An interesting tidbit it in relates to lack of effectiveness of switching thiamine-deficient animals to a ketogenic diet. You would think that taking away carbs and switching to a fat-based diet would feed the system by side-stepping the pyruvate roadblock but no.

Additionally, in the 2nd chapter of the extremely complex new book by Dr. D. Lonesdale there is something about "promiscuity" (genetic and epigenetic alterations) of certain (G and Muscarinic) receptors which I couldn't understand well.
For some reason, this chapter is not accessible in my preview and the book is ridiculously expensive on amazon. Any chance of a screenshot of the relevant page?
 

alicec

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Additionally, in the 2nd chapter of the extremely complex new book by Dr. D. Lonesdale there is something about "promiscuity" (genetic and epigenetic alterations) of certain (G and Muscarinic) receptors which I couldn't understand well.
The G and M receptors are glucocorticoid and mineralocorticoid receptors respectively.

The steroid hormone promiscuity that he is talking abut refers to the fact that many of these hormones bind to both the GRs and MRs.

The epigenetic and genetic effects he refers to affect the sensitivity of the receptors to different steroids.
 

sb4

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An interesting tidbit it in relates to lack of effectiveness of switching thiamine-deficient animals to a ketogenic diet. You would think that taking away carbs and switching to a fat-based diet would feed the system by side-stepping the pyruvate roadblock but no.
This is very interesting to me. My gastroparesis hasn't been as bad over last few weeks so I have been trying to get back into ketosis (last in 1.5years ago) but experienced major exaserbation of my POTS symptoms. I have read posts by you and others who were helped by transdermal thiamine which I started yesterday.

Had you noticed any diference with ketosis before vs after thiamine?
 

Sidereal

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This is very interesting to me. My gastroparesis hasn't been as bad over last few weeks so I have been trying to get back into ketosis (last in 1.5years ago) but experienced major exaserbation of my POTS symptoms. I have read posts by you and others who were helped by transdermal thiamine which I started yesterday.

Had you noticed any diference with ketosis before vs after thiamine?
I don't do ketosis or thiamine anymore and have never tried them together but I see no logical reason why thiamine would help with a high fat diet.
 

sb4

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I don't do ketosis or thiamine anymore and have never tried them together but I see no logical reason why thiamine would help with a high fat diet.
Okay. May I ask why you stopped?

Also I'm opening and mixing a capsule of allithiamine with different body creams but am always left with a decent amount of white powder residue which has to be allithiamine. Am I doing this right?
 

Sidereal

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Okay. May I ask why you stopped?

Also I'm opening and mixing a capsule of allithiamine with different body creams but am always left with a decent amount of white powder residue which has to be allithiamine. Am I doing this right?
Well I don't want to repeat myself. I've written about my experiences with both ketosis and thiamine at length on this forum, just do a search.

Yes, there's always some residue on the skin but enough of it gets absorbed to feel a noticeable effect within 15 minutes or so. It wears off after a few hours.
 

Sidereal

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Chris Masterjohn explained that dietary B1 intake in keto is low and why it is still needed in ketosis here: Part 1 & Part 2
I don't doubt that all vitamins are needed regardless of what diet you're on. But the question was whether supplemental thiamine enhances the benefits of ketosis.

Good to see paleo advocates acknowledging these issues. Years ago I developed terrible beriberi symptoms after long-term keto, btw, because that diet is so deficient in B1 and at the time the response was denial that such a thing is even possible because meat is the magical perfect food that contains all the nutrients you need, or something. :lol:
 

JasonUT

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I started Lipothiamine TTFD on 7/23 at 50 mg and worked up to 50 mg TID as of yesterday, 7/31. Things feel different, but I think it is far to early to pass judgement. I don't know a reasonable time frame for replenishing Thiamine via TTFD. How long does this take? How do I determine correct therapeutic dosage?

Page 14 of the paper that @Gondwanaland attached:
In birds “reversed” with thiamine treatment, the total number of myelinated nerve
fibers in the sciatic and brachial nerves increased as the birds recovered. Complete
recovery took 6–9 weeks in birds in which leg weakness had lasted for 7–10 days
before instituting treatment. This is in contrast to the rapid recovery (hours) in
rats reversed with thiamine therapy. Microscopically, dorsal ganglia continued to
show chromatolysis until symptoms cleared. It seemed that complete regeneration
of nerve fibers had to occur before symptoms disappeared.
 

Alvin2

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I started Lipothiamine TTFD on 7/23 at 50 mg and worked up to 50 mg TID as of yesterday, 7/31. Things feel different, but I think it is far to early to pass judgement. I don't know a reasonable time frame for replenishing Thiamine via TTFD. How long does this take? How do I determine correct therapeutic dosage?

Page 14 of the paper that @Gondwanaland attached:
I wonder too, if thiamine supplementation is going to increase pyruvate dehydrogenase how long to see results?
 

Chocolove

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I don't know a reasonable time frame for replenishing Thiamine via TTFD. How long does this take? How do I determine correct therapeutic dosage?
@JasonUT According to Dr. Antonio Constantini's M.D. work treating humans with forms of thiamine who have various conditions (in conjunction with medical studies) the time can of course vary. From viewing the articles and videos previously posted regarding patients with Parkinson's Disease (see post #213 for links), I gather that visually obvious results take months. However Dr. Constantini has also treated people for other conditions using thiamine.

I'm sure recovery time must vary depending on the state of the individual at beginning of treatment. If one is deficient in magnesium which is required for the body to utilize thiamine, it may take months to just replete magnesium...which is a common problem.

You can see what Dr Constantini uses with regard to dosage and check Dr. Lonsdale's treatments as well. For you the time and dosage will be what your own body decides. If you feel response is slow, I would look for something in your diet/drink or drug/supplement regimen that is depleting nutrients from your body. If it gives a bad reaction, I would back off and research what is going on. Apparently nerves do take a while to recover compared to say broken bones.

I am not a doctor. I am merely discussing my observations from review of literature and my own personal experience. I am very grateful to Dr. Constantini and Dr. Lonsdale for their work in nutrient, specifically thiamine, repletion. Their works are well worth study.
 

Chocolove

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I don't know a reasonable time frame for replenishing Thiamine via TTFD. How long does this take? How do I determine correct therapeutic dosage?
@JasonUT You may be interested in several people's experience:

...I found it interesting that, when given a blood test, many of the people in these studies had normal blood concentrations of thiamine, yet they experienced significant symptom improvement when taking high doses of thiamine. The study authors speculate that this "may indicate a dysfunction of intracellular thiamine transport or structural enzymatic abnormalities."...

Overcoming Fibromyalgia Fatigue - My Human Guinea Pig Experience

Once I was convinced that thiamine would be relatively safe for me to try, I decided to follow the basic protocol used in the FM (Fibromyalgia) study. Those patients started at 600 mg/day and increased the dosage by 300 mg every three days until they reached a therapeutic dose.

(The reason for waiting three days to increase the dose is because it can take up to 48 hours to experience the effects from an increased dose of thiamine.)

The first patient reported dramatic improvement at 600 mg. The other two did not experience any changes until they reached a dose of 1500 mg. The final therapeutic dose for both was 1800 mg, at which time they reported an abrupt improvement.

Since I couldn’t find thiamine in 300 mg tablets, I worked in 500 mg increments. Within 24 hours of getting to the 1500 mg dose, I noticed a huge increase in my energy level. I then tried taking 2000 mg to see if it made even more of a difference, but I actually felt a little worse, so I dropped back to 1500 mg/day and have remained there ever since.

I’ve been taking 1500 mg of thiamine each day for about six weeks and I can honestly say that my energy level now is much better than it has been in 24 years!
From: https://www.healthcentral.com/article/overcoming-fibromyalgia-fatigue-my-personal-experiment
http://www.bing.com/cr?IG=31E9805CB...ry/showarticle.cfm?libid=18187&p=DevEx,5032.1
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Warning: As noted by others in this forum in several threads regarding thiamine, repletion can get tricky and is not always smooth sailing. Among other requirements, B vitamins often require other B vitamins in sufficient quantities to process. If one B is taken in too great a relative quantity it may deplete others with noticeably unpleasant consequences.

High dose vitamin B1 (thiamine) | Phoenix Rising ME / …
forums.phoenixrising.me › … › Alternative Therapies
  • 20 posts · First post: Dec 15, 2014
Apr 24, 2015 · High dose vitamin B1 (thiamine) ... as there is documented evidence that high-dose thiamine can deplete riboflavin. (From a book called "Nutrient ...
 

Chocolove

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@JasonUT According to Pharmacist Dr. Izabella Wentz, aka The Thyroid Pharmacist, who shares her own personal experience repleting thiamine:

The Missing Link to Thyroid Fatigue:
Unfortunately, standard lab tests for thiamine deficiency will not show if someone is mildly deficient, they will only show a severe deficiency of thiamin.

If you’ve been struggling with fatigue, low stomach acid, carbohydrate intolerance, low blood pressure and your adrenals, you may have thiamine deficiency...

... Italian clinicians Dr. Antonio Costantini and nurse Maria Immacolata Pala, have hypothesized that the chronic fatigue that accompanies inflammatory and autoimmune diseases may be a result of a mild thiamine deficiency. They had already found that thiamine helped relieve the fatigue in people with Ulcerative Colitis (an autoimmune condition that affects the gut) and decided to try using thiamine in three women with Hashimoto’s, who were on thyroid medications but continued to experience fatigue.

...All of the women were given a survey to rate their fatigue before starting the thiamine, and again the same questionnaire 20 days into the treatment. All three reported that they experienced a relief in their fatigue during the second survey, and two had a complete remission of their fatigue!

Interestingly, none of the women had thiamine deficiency on standard lab tests that are used to measure thiamine status.

..Food sources of Thiamine include fortified grains, beef liver, and pork, dried milk, eggs, legumes and peas, nuts and seeds. Basically, with the exception of liver and pork, most of the foods that contain thiamin are restricted on the Paleo diet, and all of them are restricted on the autoimmune Paleo diet!

...Long term thiamine deficiency in those who consume any carbohydrates (even fruit) can lead to a build-up of pyruvic acid, which is a byproduct of glucose metabolism and can lead to mental fog, difficulty breathing and heart damage. Those on low-carbohydrate diets, are at a smaller risk of the build-up of pyruvic acid and may not have any symptoms, except for fatigue.

..In pharmacy school, we learned that Thiamine is a rare nutrient deficiency...

...A few days after starting thiamine, my energy began to bounce back, my blood pressure normalized, and I was able to reduce my dose of Betaine with Pepsin, which I had been taking to help me digest proteins.
From: https://thyroidpharmacist.com/articles/thiamine-and-thyroid-fatigue/
 

Chocolove

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Chocolove

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@JasonUT With regard to determining appropriate dosage of thiamine:

Enter Dr. Antonio Costantini in Italy 200 years after James Parkinson’s diagnosis. He discovered that patients suffering neurodegenerative illnesses were all vitamin B1 (thiamine) deficient.

Dr. Constantini has successfully treated 250 Parkinson’s patients since 2011 with heavy doses of thiamine...

All autoimmune diseases have chronic exhaustion as a symptom. And it was helping a patient with chronic exhaustion and an acute ulcer that set the doctor on the path to his Parkinson’s treatment. He advised her to treat herself with an injection of 2 mg of thiamine per week.

Within two weeks the patient “was relieved of exhaustion, irritability, pain in her feet and calves,” Dr. Costantini says, “Because there is no medicine or drug that is able to affect all of the organs, whereas all of the organs function thanks to Thiamine. An important detail, the Thiamine therapy brings no collateral damage with time”...

After seeing the progress made by treating his patients suffering from chronic ulcers, multiple sclerosis and similar afflictions, Dr. Costantini decided to expand his research into sufferers of neurodegenerative diseases like Parkinson’s...

In 2011 our team was working with dosages based on the body weight: 60 Kg corresponded to 600mg of vitamin B1, to be taken orally and yielding marvelous results: the elimination of exhaustion and all the symptoms that accompany it”. QUOTE]
From: https://easyhealthoptions.com/italian-doctor-curing-parkinsons-disease-with-thiamine/
http://www.ultimaedizione.eu/costan...-thiamine-parkinson-suffers-a-terrible-strik/

First therapeutic trials report

In 2013 the first reports were published the use of high-dose thiamin among Parkinson’s disease sufferers resulted in considerable improvement in measured motor function (31.3% to 77.3%). Injection of high-dose thiamin was effective in reversing symptoms. [BMJ Case Reports 2013]

Then another study published in 2015 confirmed that injectable thiamin treatment (100 mg twice a week) improves motor nerve function among Parkinson’s patients. [Journal Alternative Complementary Medicine 2015]

In 2016 researchers in Italy reported on the successful use of high-dose thiamin among Parkinson’s patients. Notably, all of the patients had normal blood levels of thiamin yet thiamin therapy led to significant improvement in Parkinson’s symptoms. There were no adverse events. [Neural Regeneration Research2016]...

According to the US Department of Agriculture (USDA) nutritional deficiencies are rampant in over-fed/undernourished America. Just a sampling from the USDA list of essential nutrients that are not consumed in sufficient amounts by a percentage of the population includes vitamin E (86.4%), folic acid (40.3%), magnesium (57%), potassium (92.4%), vitamin C (42%), zinc (29.2%). [Knowledge of Health]

The digestive tract of over half of the US population is infected with Helicobacter pylori, a bacterium that shuts off the cells that secrete acid necessary for nutrient absorption. [Minerva Gastroenterologica Dietologica 2011]

Western populations are paying a high price for poor absorption or depletion of thiamin due to consumption of alcohol, drugs like diuretics (water pills), refined sugar, carbohydrates, even coffee and tea. [Evidence Based Complementary Alternative Medicine 2006]

The ordeal of undetected thiamin deficiency is only exacerbated by the modern paradigm of treating symptoms of disease as if they emanate from the drug deficiency, not a nutrient deficiency...

So we now have 60,000 Americans diagnosed with Parkinson’s disease annually and 10 million worldwide living with the disease. More than 23,000 die of Parkinson’s disease annually in the U.S. [Parkinsons Disease Foundation]

Levodopa, the main drug prescribed for Parkinson’s disease, costs ~$2500/year. [Parkinson’s Disease Foundation]

As of 2014 there were 23 medicines under development for Parkinson’s disease. Drugs only serve as a distraction for a disease that may emanate from a vitamin deficiency.

Thiamin deficiency is associated with other age-related brain diseases such as Alzheimer’s and Huntington’s disease. [The Scientist Oct 2013]...

As for the doctor in Italy who has reported on the successful use of thiamin/vitamin B1 for Parkinson’s disease symptoms we can only say bravo and wonder when the Nobel Prize committee will take notice.
From the well referenced article: https://www.lewrockwell.com/2017/01/bill-sardi/doctor-italy-quells-parkinsons-disease/