Thiamine

Thiamine (Vitamin B1) is a B complex vitamin important in the metabolism of energy from carbohydrates, the production of RNA and DNA, and nerve function.

Thiamine pyrophosphate (TPP) is part of the conversion of acetyl coenzyme A (CoA).

The symptoms of thiamine deficiency include fatigue, paresthesia, muscle weakness, nausea, changes in heart rate, and delirium. Derrick Lonsdale and Chandler Mars argue that thiamine deficiency is more common than generally understood and an important contributor to dysautonomia. Without adequate and usable thiamine intake, the citric acid cycle necessary for aerobic respiration cannot be completed. In its extreme forms, thiamine deficiency manifests as beriberi and Wernicke's encephalopathy.

High-Dose Thiamine
In a series of small case studies published between 2013 and 2018, Alberto Costantini and colleagues found that high doses of thiamine substantially reduced fatigue in people with a range of neurological and inflammatory conditions, including Parkinson's Disease, Multiple Sclerosis, Fibromyalgia, Inflammatory Bowel Disease, and cluster headaches. Costanini and colleagues generally reported amounts between 600 and 1,800 mg of oral thiamine hydrochloride in their case studies, eventually articulating a dosage regime based on weight and gender. (They have developed a different dosage for Parkinson's Disease.) In 2020, Bager and colleagues applied a similar approach in a double-blind crossover randomized controlled trial, finding 600 to 1,800 mg of oral thiamine hydrochloride to be effective in relieving fatigue in patients with quiescent IBD. Bager and colleagues found that the reductions in fatigue were not limited to patients with thiamine deficiency, a result also found by Costantini and colleagues.

In their articles on high-dose thiamine, Costantini and colleagues offered a number of explanations for why high-dose thiamine might reduce fatigue, including a hypothesis that high doses of thiamine might be compensating for defects in the active transport mechanism that allows thiamine to enter the cell and be used by the mitochondria to produce energy. Under this hypothesis, which Bager and colleagues also posit, large doses of thiamine are necessary to allow blood thiamine levels to rise to the point where thiamine could enter the cells through passive diffusion.

An alternative explanation, summarized in a letter to the editor commenting on the Bager study, focuses on high-dose thiamine's property as a carbonic anhydrase inhibitor, which has been proven in vitro, though not yet studied in vivo. As hypothesized in the letter, "The inhibition of carbonic anhydrase isoenzymes by high-dose thiamine and the resulting production of carbon dioxide could lead to reductions in fatigue and other symptomatic improvement through one or more of four potential pathways: (a) by reducing intracranial hypertension and/or ventral brainstem compression; (b) by increasing blood flow to the brain; (c) by facilitating aerobic cellular respiration and lactate clearance through the Bohr effect ; or (d) by dampening the pro-inflammatory Th-17 pathway, again through the Bohr effect, potentially mediated by reductions in hypoxia-inducible factor 1. ". A more complete explanation of this hypothesis can be found here.

Studies have also examined the potential of the thiamine derivative, sulbutiamine, to reduce fatigue.

Chronic fatigue syndrome
One very small study found decreased functional status of several B vitamins including pyridoxine, riboflavin and thiamine.

To date, high-dose thiamine has not been studied formally in patients with ME/CFS. However, an informal retrospective survey on the use of 200 mg or more daily of thiamine among 55 individuals with ME/CFS, Fibromylagia or Ehlers-Danlos Syndrome was reported in Health Rising in 2021. Among the 55 individuals responding to the survey -- 49 of whom reported having ME/CFS -- nearly two-thirds reported large benefits from high-dose thiamine, with another 5 percent reporting smaller benefits. The most commonly reported benefits were reductions in fatigue, post-exertional malaise and brain fog. While the incidence of side effects was generally low, and most people reporting mast cell activation syndrome (MCAS) reported benefitting from high-dose thiamine, a number of respondents reported that high-dose thiamine made their MCAS symptoms substantially worse, suggesting that caution be exercised by those with severe MCAS or active flares.

For further discussion of the potential of high-dose thiamine to help people with ME/CFS, Fibromyalgia, and the neurological complications of Ehlers-Danlos Syndrome, see these resources.

Formal research is needed on the potential of high-dose thiamine to benefit people with ME/CFS.

Type of Thiamine
There are a number of different forms of thiamine used in supplements. The most common forms are thiamine hydrochloride, thiamine mononitrate, and benfotiamine. Benfotiamine is reportedly better absorbed than the other two forms, but a study of the pharmacokinetics of thiamine hydrochloride found that when taken regularly, oral thiamine hydrochloride produced blood levels similar to that of intravenous administration.

Several thiamine derivatives are reported to cross the blood-brain barrier, including sulbutiamine and allithiamine.

Learn more

 * Linus Pauling Institute Micronutrient Information Center - Thiamine