⌬

High dose thiamine therapy changed my life. I have recommended this versatile B vitamin to many people for many different reasons. Throughout my own experience with it, I have learned a lot and received a lot of questions, so I have taken the time to organize all the answers here. Disclaimer: I am not a doctor and this is not medical advice. Thiamine Therapy FAQs 1. What is thiamine? Thiamine, or vitamin B1, is a water-soluble vitamin and, as the "1" implies, the first water-soluble vitamin ever discovered. It was found in 1910 by Japanese agricultural chemist Umetaro Suzuki but it wasn't until 1934 that its structure was determined by Robert Runnels Williams. It was named by the Williams team as a portmanteau of "thio" (sulfur-containing) and "vitamin". Modern spellings of thiamine often omit the "e" since it is not an amine as was previously thought, but still the spelling with the "e" remains the most common. Thiamine is necessary for: • Energy metabolism • Nervous system function • Cardiovascular health • Cellular function • Digestive health • Muscle function • Immune function • Hormone health • Detoxification Conditions improved with thiamine supplementation include: • Beriberi • Wernicke-Korsakoff syndrome • Depression • Shingles • Cataracts • IBS • IBD • POTS • CFS • MS • MCAS • Sleep apnea • Parkinson's • Alzheimer's • Autism • Fibromyalgia • Diabetes • Dysautonomia • Cancer These are all metabolic illnesses, or illnesses which have a major metabolic component, and thiamine is crucial for metabolism. 2. What is the difference between the different forms? The active form of thiamine is thiamine pyrophosphate (TPP), and it is this form that makes its way into the cell. The most common forms of supplemental thiamine are thiamine hydrochloride (B1 HCl) and thiamine mononitrate (TMN)—these are low-bioavailability salt forms. More potent forms of thiamine were developed in Japan in the '50s, and these consist of TTFD, benfotiamine, sulbutiamine, allithiamine, and prosultiamine, among others. Some of these are naturally occurring (allithiamine), while others are synthetic (TTFD, benfotiamine, sulbutiamine, and prosultiamine). These potent forms are often considered "fat-soluble", although this classification is not entirely accurate. Technically, these forms are still water-soluble, but their chemical structure allows for greatly increased permeability through the cell membrane as if they were fat-soluble. What makes these "fat-soluble" forms so unique is their ability to bypass the need for transporter proteins (ThTR1, ThTR2), making them effective in people who have thiamine transport issues. 3. What can cause a thiamine deficiency? • Refined carbohydrate intake* • High intake of coffee, teas, and raw fish** • Alcoholism • Kidney disease • Diabetes • Diarrhea • Metformin • Antibiotics (Flagyl) • Diuretics • Metabolic disease • Digestive issues • Surgery • Stress *This does not make carbohydrates inherently bad, it is simply a metabolic reality that carbohydrate metabolism needs thiamine. **These contain thiaminases, or enzymes that break down thiamine. This does not make coffee, tea, or raw fish inherently bad, but it is something to keep in mind if one is consuming these regularly. 4. Why such a high dose? Because of the generality of potential symptoms, thiamine deficiency is greatly underdiagnosed. Thiamine deficiency can be brought on by a "functional deficiency", where oxidative stress and inflammation block enzymes that use thiamine or destroy the molecule entirely. There are also regional deficiencies that are localized to just the brain, the heart, or the digestive system. In some people, transport proteins can be deficient or defective. In such a circumstance, either larger doses or more potent forms are necessary. Part of the high-dose therapy is the aspect of total saturation—using the vitamin in supraphysiological doses, making it drug-like, and helping the body to "remember" how to use this crucial nutrient. Unlike pharmaceuticals, however, this "drug-like" use of thiamine is much safer than patented drugs. 5. Which enzymes need thiamine? • Pyruvate dehydrogenase, a rate-limiting step in glucose oxidation and the "key" for entry into the Krebs cycle from glycolysis (a crucial step in breaking down carbs) • α-Ketoglutarate dehydrogenase, another rate-limiting step, this time in the Krebs cycle, which involves the metabolism of the 3 main fuel substrates (carbs, fats, and proteins) • Branched-chain ketoacid dehydrogenase, needed to process branched-chain amino acids from protein • Transketolase, the enzyme which connects the pentose phosphate pathway to glycolysis, crucial for antioxidant defenses and damage repair 6. How bioavailable are the different forms? • Thiamine hydrochloride (B1 HCl), 3-10%* • Thiamine mononitrate (TMN), 3-10%* • TTFD (thiamine tetrahydrofurfuryl disulfide, also known as fursultiamine), 50-90% • Sulbutiamine, 50-90% • Benfotiamine, 50-90% *Due to passive diffusion, doses above 500 mg will increase the bioavailability, however, opting for B1 HCl over TMN due to the latter's nitrate content would be preferable. 7. Which forms cross the blood-brain barrier? • B1 HCl*, limited entry • TMN*, limited entry • TPP**, limited entry • TTFD, crosses BBB • Sulbutiamine, crosses BBB • Benfotiamine, crosses BBB *While B1 HCl and TMN cannot cross the BBB, bolus doses can increase bioavailability due to passive diffusion. People with serious neurological issues like Parkinson's have been shown to get relief from 2 - 4 grams of B1 HCl, so it should not be written off for being "low bioavailability". **TPP is the active form of thiamine but when supplemented orally, it reaches the intestine and is converted back into normal thiamine. However, phosphorylated forms of thiamine such as TMP and TDP can cross the BBB. 8. What is the best form? There is no best form of thiamine; it is entirely dependent on a person’s individual needs. A good form to start with is B1 HCl: it’s cheap, least likely to provoke a "paradoxical reaction", and can accustom one to thiamine so that one feels more ready to try potent forms. 9. What is the best dose? This is another impossible question to answer. Not only regarding thiamine, but with most any supplement that is correcting a metabolic problem. The amount of thiamine needed to fix metabolic problems is so widely variable that it would be useless to know how much helped someone else. However, there are effective dose ranges: • B1 HCl, 500 mg - 4,000 mg • TTFD, 100 mg - 800 mg • Benfotiamine, 300 mg - 1,000 mg Use common sense: start low and titrate up slowly. Never take more than one new supplement at a time to keep track of what is doing what. Additionally, the upper ranges listed for TTFD and benfotiamine will rarely need to be reached. 10. When is the best time to take thiamine? At least 30 minutes after the first meal of the day with plain or sparkling mineral water. If taking a second dose, 30 minutes after lunch. Some find that thiamine helps with sleep, but taking it at night is less common due to it being mentally stimulating. 11. Is there a dosage-equivalence between different forms? There is not enough available data to answer this question. Based on bioavailability estimates, one can assume benfotiamine and TTFD are similar, but these are not equivalent in their action. Elliot Overton has observed lower doses of TTFD achieving similar effects to higher doses of benfotiamine. Although this is anecdotal, it is worth keeping in mind. 12. How long to take thiamine for? Yet again, it is entirely dependent on the person’s unique physiology and circumstances! Some take a high dose for 3 - 6 months and find that they can taper down to nothing; others use thiamine on an as-needed basis for mentally or physically demanding tasks; and still others need to take it for life, as in the case of serious neurological illnesses like Parkinson's. Still, taking a relatively inexpensive and widely available B vitamin is preferable to relying on a patented pharmaceutical with a concerning list of side effects. 13. Does high-dose thiamine therapy increase the need for other nutrients? Yes. HDT therapy may increase the need for: • B2 • B3 • B5* • B6 • B7* • B9 • B12* • Salt • Magnesium* • Potassium • Copper • Selenium • Molybdenum* • CoQ10* • Glutathione* *These tend to be the nutrients put under the most pressure by thiamine. Is the solution to panic and start taking all of these supplementally? Definitely not. Eat a balanced diet, start with a B complex, add in magnesium, and go from there. Additional troubleshooting may or may not be required down the line. Thiamine HCl is the easiest to titrate up and typically involves the least troubleshooting. Disulfide derivatives (TTFD, allithiamine, sulbutiamine, and prosultiamine) may put pressure on sulfur metabolism which may be remediated with CoQ10 and/or molybdenum. 14. What about brewer's yeast? Nutritional yeast? Nutritional yeast and brewer's yeast both contain phytoestrogens and can cause gut upset when used supplementally at the frequency needed for high dose thiamine therapy due to their probiotic content. It is possible to boil off the phytoestrogens and probiotics, but it would be more practical to use a quality B complex supplement. 15. Can thiamine deficiency be tested for? Currently, there are five methods to measure thiamine status, however, not all or accurate or practical: • Blood thiamine • Urinary thiamine excretion • Pyruvate and lactate • Whole blood high-performance liquid chromatography (HPLC) • Erythrocyte transketolase activity/thiamine pyrophosphate effect (ETKA/TPPE) Blood thiamine is the most common thiamine test and is useless because it only shows whether or not thiamine was ingested recently. The blood contains only 0.8% of total body free thiamine, making this test not at all reflective of tissue levels. Concentration of thiamine in the blood or plasma can be completely normal even in an advanced deficiency. It is likely a doctor's first choice if their patient tells them they are concerned about a thiamine deficiency, though. Urinary thiamine excretion is a similar story. Since thiamine is required for pyruvate metabolism, elevated pyruvate and lactate can be a sign of thiamine deficiency. HPLC is one of the newest methods of testing and it is used to measure thiamine, TPP, and its esters in the erythrocytes. HPLC is more accurate than blood or urine tests and more able to identify the early stages of a thiamine deficiency, however, it is costly and not easy to order. The most accurate thiamine test available to the general public, therefore, is the ETKA/TPPE: a pair of tests which assess thiamine usage and reflect stores at the tissue level. • First, baseline transketolase activity (TKA) is measured in international units per liter of blood per unit of time (normal ranges being between 42-86 mU/L/min). • Next, TKA is repeated after active thiamine (TPP) is added to the reaction medium. • If TKA increases, it is taken as proof that the enzyme was not saturated with its cofactor. • This is reported as the percentage increase over base activity and is known as the “thiamine pyrophosphate effect”, or TPPE (normal ranges being 0% - 18%). Derrick Lonsdale and Chandler Marrs have made some useful observations on ETKA/TPPE results: • Sometimes the TKA is low while the TPPE is normal and this would suggest abnormality in the TKA enzyme. • In most cases of thiamine deficiency, the TPPE is increased, sometimes remarkably so, while the TKA is in the normal range. • In a more severe deficiency state, the TKA is low, but in the normal range, and the TPPE is high. "Correlating the patient's symptoms with a fall in the TPPE and a rise in TKA (remaining within the normal range) is an excellent way of proving the clinical effect of thiamine supplementation," they conclude. While the ETKA/TPPE is the best test for thiamine deficiency, even this test is imperfect. With this in mind, it is best to try thiamine regardless because of how low risk it is. 16. How to tell if thiamine is working? Generally, whether thiamine is working or not is obvious. For many—especially when higher doses are reached—the difference is night and day. For others, they may have paradoxical reactions or need to dial in other nutrients which thiamine may put undue pressure on. If someone wanted to be sure thiamine was helping, buying an at-home lactate meter (such as the Nova Biomedical Lactate Plus Meter) to see whether thiamine raises or lowers lactate would be reasonable. 17. Which products to take? • B1 HCl - Pure Bulk, Dr. Clark Store • TTFD - Objective Nutrients ThiaMax* • Mixed - Objective Nutrients ThiaMega* • Benfotiamine - Bulk Supplements • B Complex - Objective Nutrients ThiActive methylated B complex, Premier Research Labs Complete B, -Pure Encapsulations B-Complex Plus, Dr. Clark Store Super B100 *If you feel you are ready to try the most potent forms of thiamine, use code "TAKETHIAMINE" for 10% off your order at Objective Nutrients. The only quality TTFD product without excipients on the market is ThiaMax, and I trust it enough to take daily. 18. Additional resources? • Dr. Antonio Costantini's YouTube channel • Elliot Overton's YouTube channel • Elliot Overton's protocols for addressing thiamine deficiency & the paradoxical reaction PDF • Hormones Matter blog • "Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition" by Derrick Lonsdale and Chandler Marrs • Chris Masterjohn's Energy Metabolism Masterclass

Little dude delivers a wicked uppercut!

presented without comment

'Male masturbation may have an adaptive benefit: it flushes out damaged, stored sperm.' New Oxford research suggests that the longer sperm are stored before ejaculation, the lower their quality, with implications for men trying to conceive and IVF treatment. Find out more ⬇️

Asparagus is my favorite tool for dieting Contains the amino acid asparagine, which has mild diuretic properties which help push out excess sodium from the body This is an old bodybuilding used for years that you can also utilize Because asparagus increases urinary sodium excretion, which shifts systemic balance Your cells will then follow the gradient..