Invest in ME Conference 12: First Class in Every Way
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Pyruvate dehydrogenase function depends on thiamine (B1)

Discussion in 'General Treatment' started by Chocolove, Jan 14, 2017.

  1. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    Pursuant to the research: Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS

    It should be noted that the pyruvate dehydrogenase function is dependent upon thiamine (B1), a deficiency of which could be of serious concern in ME/CFS.

    "Humans store between 25-30mg of thaimine, much less than other animals. Due to thiamine being a water soluble nutrient, depletion can occur in 14-18 days."

    "Cellular roles of Thiamine

    Thiamine has several roles in cellular glucose metabolism as it functions as a cofactor for various enzyme complexes. The pyruvate dehydrogenase(PDH) and alpha ketoglutarate dehydrogenase(a-KGDH) enzyme complexes are important thiamine dependent enzyme complexes that help liberate energy from glucose in the citric acid cycle of mitochondria.

    During glycolysis in the cytosol, glucose is converted in to 2 pyruvate molecules that enter the mitochondria. Inside the mitochondria, pyruvate is converted in to acetyl CoA by the PDH complex so that it can enter the citric acid cycle. This step requires thiamine diphosphate as a coenzyme.

    This is important for 2 reasons. In neurons, acetyl CoA comes predominantly from glucose and is necessary for the synthesis of the neurotransmitter acetylcholine, which we will cover later.

    Secondly, in all cell types, insufficient thiamine decreases PDH activity and lactate accumulates in the cell and pours out in to the circulation. Blood lactate is known to be elevated in Type 2 diabetics(2) and high blood lactate levels induce insulin resistance in skeletal muscle(3)."

    "The role of a-KGDH in the citric acid cycle is also of importance as this enzyme complex is necessary for the synthesis of the neurotransmitters GABA, glutamate, and aspartate. Furthermore, the altered glucose metabolism that accompanies a deficiency in the activity of PDH and a-KGDH can lead to mitochondrial damage and eventual cell death(4)."

    "Another area of glucose metabolism where thiamine is important is the pentose phosphate pathway. The pentose phopshate pathway is an anabolic pathway of glucose metabolism that creates NADPH or R5P based on cellular needs. For a more thorough look at this process, check out this blog. Understanding the pentose phosphate pathway is crucial for understanding hormonal balance and how adrenal function can be affected by thiamine deficiency so I urge you to check that blog out."

    "One study showed that inducing thiamine deficiency in rats led to hyperstimulation of the zona fasciculata of the adrenal glands in 2 weeks causing increased corticosterone output followed by complete exhaustion in 4 weeks(8)."

    "A study in humans found thiamine injections prevented functional adrenal gland exhaustion during and after surgical stress(10) "

    The above quotes and further details are found at :
    http://synergyhw.blogspot.com/2015/04/the-importance-of-addressing-thiamine.html

    Got Thiamine - (B1)?
     
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  2. hixxy

    hixxy Senior Member

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    Haven't vitamins already been done to death? Truly...
     
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  3. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    Check out the article. Think you will find it very informative.
     
  4. Mary

    Mary Senior Member

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    @Chocolove - I don't have the energy right now to try to make sense of the technical aspects of what you wrote; however, thiamine did increase my energy. I had been taking a B complex for years and years, but turns out I needed more thiamine, which I only realized relatively recently (within the last 9 months I'd say). No, vitamins have not been done to death! It's truly amazing to me the effects some of these supplements, even when I tihnk I've tried everything, I keep learning new things. If we knew everything, we'd be cured.
     
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  5. eljefe19

    eljefe19

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    Just started allithiamine today! :)
     
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  6. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    Are you vitamin B1 deficient?

    First off, vitamin B1 levels decline with age. However, as previously noted, deficiency is most commonly found in those with poor diets, those who eat sugar & refined carbohydrates, those using excessive caffeine, those regularly using common medications, those under stress, those with chronic fatigue syndrome, alcoholics, diabetics, people with malabsorption conditions following gastric bypass surgery, & children with congenital heart disease. Vitamin B1 deficiency is prevalent in those with Autism & ADHD.

    Individuals undergoing regular kidney dialysis may develop severe vitamin B1 deficiency and should discuss the need for vitamin B1 supplementation with their physician.

    Thiamine deficiency can also occur when excess vitamin B1 is used up by the body. This can be caused by:
    • Pregnancy
    • Hyperthyroidism
    • Lactation
    • Fever- Severe infection/sepsis
    • Increased physical exercise
    • Refeeding syndrome (is a metabolic complication that occurs when nutritional support is given to severely malnourished patients)
    Inadequate thiamine intake can occur via diets consisting mainly of the following:
    • Food containing a high level of thiaminases (which impair thiamine), including milled rice, raw freshwater fish, raw shellfish, and ferns
    • Food high in anti-thiamine factor, such as tea, coffee, and betel nuts
    • Sulfites are added to many processed foods as a preservative. Sulfites destroy thiamine
    Certain medications can deplete vitamin B1. These include:

    *Acid Blockers: Cimetidine (Tagamet), Esomeprazole (Nexium), Famotidine (Pepcid & Pepcid Complete), Lansoprazole (Prevacid 24hr), Nizatidine (Axid), Omeprazole (Prilosec OTC), Pantoprazole (Protonix), Rabeprazole (Aciphex), Ranitidine (Zantac)

    *Antacids: Aluminum & magnesium hydroxide (Maalox, Mylanta), Aluminum carbonate gel (Basaljel), Aluminum hydroxide (amphojel, AlternaGEL), Calcium carbonate (Rolaids, Titralac, Tums), Magnesium hydroxide (Phillips’ Milk of Magnesia), Sodium bicarbonate (Alka-Seltzer, baking soda)

    *Antibiotics (just a few listed here, but all deplete vitamin B1: Aminoglycosides, Amoxicillin (Amoxil), Azithromycin (Z-pak), Cefdinir (Omnicef), Cephalexin (Keflex), Ciprofloxacin (Biaxin), Doxycycline (Doryx), Erythromycin (E.E.S.), Levofloxacin (Levaquin), Minocycline (Minocin), Penicillin (Pen VK), Sulfamethoxazole & trimethoprim (Bactrim, Septra), tetracycline (Sumycin)

    *Anticonvulsants: Phenytoin (Dilantin) space supplement at least 4 hours away from the medication, Zonisamide (Zonegran)

    *Antivirals: Delavirdine (Rescriptor), Lamivudine (Epivir), Nevirapine (Viramune), Foscarnet (Foscavir), Zidovudine, AZT (Retrovir), Zidovdine & lamivudine (Combivir)

    *Aromatase Inhibitors for breast cancer: Anastrozole (Arimidex)

    *Cardiac Glycoside: Digoxin (Lanoxin, Lanoxicaps, Digitek)

    *Blood Pressure Drugs: Bumetanide (Bumex), Ethacrynic acid (Edecrin), Furosemide (lasix), Torsemide (Demadrex), Indapamide (Lozol), Hydrochlorothiazide or HCTZ (Hyrodiuril). Any combination drug that contains HCTZ or hydrochlorothiazide (dozens of drugs contain this), Chlorothiazide (Diuril), Chlorthalidone (Hygroton), Methyclothiazide (Enduron), Metolazone (Zaroxolyn)

    *Diuretics: Loss of thiamine through renal excretion can occur with most, if not all, diuretics. It has been seen with the use of such diuretics as mannitol, acetazolamide, chlorothiazide, amiloride, and loop diuretics. Thiamine loss is associated with the increase in urine flow rate.

    *Bronchodilators: Theophylline (Uniphyl, Theo-24, or Theo-dur)

    *Hormone Replacement Therapy/Oral Contraceptives: Estradiol (estrace, Climara, Estraderm, estring, Activella, Femring, Combipatch,strogel, menostar, & many others), Estrogen-containing drugs (hormone replacement therapy & birth control), estrogens, conjugated (Premphase, Pempro), Ethinyl estradciol (found in many birth control pills)

    *Sulfonamides: Sulfa antibiotics, some diabetes medications

    *SERMs (Selective Estrogen Receptor Modulators used for breast cancer): Raloxifene (Evista), Tamoxifen (Nolvadex), Toremifene (Fareston)

    *Miscellaneous: Alcohol, coffee, estrogen dominance, genetic problems that prevent you from activating B1, quercetin & rutin, raw shellfish or raw seafood such as sushi, oysters or mussels, sulfites found in foods as a preservative, tea (because of the tannins in tea, even decaf), tobacco (nicotine)

    This information compiled from the book “Drug Muggers: Which Medications Are Robbing Your Body of Essential Nutrients--and Natural Ways to Restore Them” by Suzy Cohen
     
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  7. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @eljefe19 Hope you record and share your responses to the Allithiamine.

    "The thiamine form of B1 is water soluble and easily lost every day in your urine. But there is a fat soluble form called Allithiamine which is far more effective than the commonly available water soluble form. This form is excreted from the body at a slower rate & is more useful for protecting & promoting the health of the nervous system.

    The brain requires much more thiamine than other cells. Numerous B1 deficiency symptoms relate to the nervous system. Because brain cells & nerves have a high amount of fat, more fat soluble B1 will stay in the nervous system where it effects its numerous benefits.

    Allithiamines are found naturally in onions, garlic, leeks, and other members of the allium family of vegetables.

    Benfotiamine is the most effective metabolic precursor of active thiamine available. It has been safely used in Europe for many years. This lipid-soluble form of vitamin B-1 can enter a cell by dissolving in the lipid (fat) portion of the membrane and diffusing through it.

    Clinical studies have shown that supplementation with benfotiamine results in plasma levels 5 times higher than the usually available water-soluble thiamin. The amount absorbed into specific cellular tissues such as the brain, nerves, kidney, liver or muscle can be five to twenty-five times more than regular thiamin. Most of the thiamine in the serum is bound to protein, mainly albumin. In blood 90% of thiamine is in the red blood cells."

    The above quote comes from:
    http://www.thewayup.com/newsletters/080614.htm
     
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  8. alicec

    alicec Senior Member

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    A functional deficiency is possible because of various deranged metabolic pathways. Very high doses of B1 may be able to overcome this to some extent, but as the Fluge and Mella studies show, problems with the enzyme are not as simple as not having sufficient cofactor.

    Here and here are posts that are relevant.

    While it is often claimed that benfotiamine is an allithiamine and is fat soluble, this is not correct. See this study. Look at Fig 1 and you will see that benfotiamine does not have the characteristic dithiol structure of the allithiamines.

    As a result, it doesn't readily cross cell membranes and the BBB as does the allithiamine family. It is just another form of thiamine with no special advantages.
     
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  9. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @eljefe19 What brand of allithiamine are you trying?
     
  10. eljefe19

    eljefe19

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    @Chocolove I am using Cardiovascular Research brand. However, my results will not be scientific. I am addressing several angles of supplementation at once and the results are muddled.
     
  11. JES

    JES Senior Member

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    Benfotiamine can be used in a lot smaller dosage than thiamine while obtaining the same effects, from my personal experience. Also I've read that benfotiamine is much more useful for diabetics (diabetic neuropathy) than regular thiamine, pretty much every diabetic prefers to take the benfo form. But yeah, it won't cross BBB so in that sense allithiamine can be better, though it's much harder to find on the market and probably more expensive.
     
  12. eljefe19

    eljefe19

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    Allithiamine is on Amazon. I'm going to try 100mg x2 a day. Also have some Sulbutiamine otw. Benfo had no noticeable effect.
     
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  13. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @eljefe19 Interesting review on Allithamine:
    https://smile.amazon.com/Ecological...d=1484446598&sr=8-1&keywords=allithiamine#Ask

    5 starsRecommended if your nervous system is on the fritz. By Steve reviews stuff on January 3, 2015
    Verified Purchase
    This is amazing for autonomic nervous system function. I have POTS (postural orthostatic tachycardia syndrome -- pulse shoots up by 40 beats per minute when I stand. In my case it was not debilitating but some people are almost unable to function in the upright position due to the severity of their condition). Taking this (6 - 8 caps a day!) has mostly resolved it. Hoping some other related health issues will resolve with chronic use. Google Dr. Derrick Lonsdale and Thiamine to see more -- though some of it has the alarmist "OMG we're all thiamine deficient" tone, it is some VERY interesting research nonetheless.

    You may need to add supplemental magnesium, preferably a bioavailable form (not oxide), to make this work / avoid side effects (palpitations / anxiety). Magnesium is a cofactor for the functioning of thiamine, among its many other roles in the body. Adding a bit of the other B vitamins, particularly riboflavin, may be important also, as their functioning is generally interdependent.
    8 Comments
     
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  14. eljefe19

    eljefe19

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    Thanks @Chocolove !! I read that too. I have a touch of POTS, not major but mild. Brain fog is thick right now I will reply more comprehensively later.
     
  15. Chocolove

    Chocolove Tournament of the Phoenix - Rise Again

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    @eljefe19 You may not be able to correct a thiamine deficiency - until you satisfy Magnesium requirements.
    By some estimates, up to 80 percent of Americans are not getting enough magnesium and may be deficient. Other research shows only about 25 percent of US adults are getting the recommended daily amount of 310 to 320 milligrams (mg) for women and 400 to 420 for men.2

    Even more concerning, consuming even this amount is "just enough to ward off outright deficiency," according to Dr. Carolyn Dean, a medical and naturopathic doctor.

    As per http://www.mgwater.com/Seelig/Magnesium-Deficiency-in-the-Pathogenesis-of-Disease/chapter8.shtml

    "Thiamine loses enzymatic activity in magnesium-deficient rats, which exhibit signs of thiamine deficiency unless magnesium is repleted (Zieve et al., 1968a,b; Zieve, 1969). Furthermore, thiamine levels have been shown to fall in liver and kidneys of magnesium-deficient rats (Itokawa et al., 1974c). Magnesium-deficient alcoholics are unresponsive to vitamin B (and other B vitamins) until their magnesium is repleted (Zieve, 1975).

    Magnesium deficiency has long been recognized in alcoholism (Flink et al., 1954; Review: Rink, 1976/1980); it can be secondary to low intake, malabsorption, and, if cirrhosis develops, secondary aldosteronism (Review: Massry and Coburn, 1973). The dependence of thiamine activity on magnesium as a co-factor is relevant (not only to the psychoneurologic manifestations of alcohol withdrawal) but to at least three of the metabolic aberrations that affect the heart in alcoholism"...
     
  16. alicec

    alicec Senior Member

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    I should have said that benfotiamine is absorbed better from the gut than thiamine, hence higher blood levels may be achieved so yes, there is that advantage. However it is converted into thiamine before uptake into cells and is subject to the same limited capacity of the thiamine transporter.

    This does not apply to the lipophilic allithiamines. They get into the cell by a different mechanism and much higher intracellular concentrations are achieved. This same mechanism allows them to get into the brain.
     
    Last edited: Jan 15, 2017
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  17. Sidereal

    Sidereal Senior Member

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    The pyruvate dehydrogenase problem in ME/CFS is not caused by thiamine deficiency. Taking thiamine or other vitamins is not going to fundamentally fix anything. Taking very supraphysiologic doses of lipophilic forms of thiamine can in some cases push the busted enzyme, essentially forcing it work a bit better, thus giving the patient some symptomatic relief, but this is NOT fixing the underlying metabolic problem.

    Also, not everyone will be responsive to PDH cofactor supplementation. It's been quite hit-and-miss in my circle of friends with whom I've shared my experiences. There is a vast literature out there on the inborn error of metabolism pyruvate dehydrogenase deficiency (which is a million times more serious than ME/CFS) and the results from supplementation are very hit-and-miss. The same applies to beriberi and Wernicke's encephalopathy which are B1 deficiency diseases. It is pretty clear that regular thiamine does very little or nothing to reverse the brain problems in those conditions but there is some anecdotal evidence for efficacy of sulbutiamine and allithiamine. Unfortunately these are Japanese products and the English-language literature is almost completely devoid of knowledge. It's mostly just anecdotal stuff on the web.

    I would just add that in my personal experience taking allithiamine per se did nothing unless I also took lipoic acid around the clock, ate a very high carb nearly zero fat diet (to side-step the loss of metabolic flexibility due to PDH dysfunction; you can read about the so-called Randle cycle to understand what is happening when you have a broken metabolism and try to eat mixed meals of fat and carbs) and I also had to supplement FMN. Riboflavin got seriously depleted after just two days on this protocol. Also, when things got a little crazy taking niacin to slow things down was essential.

    Refeeding syndrome is also a serious concern and a potentially fatal outcome if you've been severely affected a long time and thus depleted of minerals/electrolytes. I ran into severe phosphate deficiency on day 3. Magnesium and calcium were also a serious problem. Fortunately, it made my longstanding hypokalemia disappear but this is another serious problem for many here and it can cause a fatal arrhythmia.

    The researcher Chris Armstrong commented on another thread that ME/CFS metabolism resembles starvation and sepsis and warned about refeeding syndrome. I think people would stand to benefit from reading his comments before playing around with active forms of thiamine.
     
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  18. eljefe19

    eljefe19

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    @Sidereal It may not be a cure, and it may all be theoretical, but if a comprehensive approach is being taken on supplementation, then co-factors like allithiamine make sense. Thiamine on its own is probably ineffective long term. But how about Thiamine plus Rituximab? Not to mention the multitudes of other supplements I use. I am considering Rituximab but I would want to stack it with the things that theoretically will shift my body back towards good health. Once my body is no longer fighting to get back to an ill homeostasis, supplying the body with thiamine, for example, I believe will get the whole PDH mess running smoothly faster and more effectively than thiamine or Rituximab on their own.
     
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  19. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Supplements help in nearly zero serious immunological disorders (or whatever this is), and is extremely unlikely to give benefit here as well. Good post Sidereal
     
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  20. eljefe19

    eljefe19

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    I'm not sure what you mean by this. I've experienced some tremendous QOL gains from supplementation. Granted, I spend hours and hours on research. My regimen is top notch. I used to be incredibly sick, severe CFS and now I am squarely moderate. Cure? No. That's why I'm pursuing Rituximab.
     
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