Editing Thiamine

'''Thiamine''' (Vitamin B<sub>1</sub>) is a [[B vitamin|B complex] vitamin]] important in the [[energy metabolism|metabolism of energy]] from [[carbohydrate]]s, 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]],[[paresis|muscle weakness]], [[nausea]], changes in heart rate, and delirium.  Derrick Lonsdale and Chandler Marrs argue that thiamine deficiency is more common than generally understood and an important contributor to [[dysautonomia]].<ref>{{Cite book | title=Thiamine Deficiency Disease, Dysautonomia, and High Calorie Malnutrition|isbn=|edition=|language=English|title-link= | url = |access-date= | date = 2017 | publisher=Academic Press | editor-last = Lonsdale | editor-first = Derrick | authorlink = |editor-last2=Marrs|editor-first2=Chandler | author-link2 = |location=Cambridge, MA|pages=213–61|doi= 10.1016/B978-0-12-810387-6.00006-X|oclc=|quote=|archive-url = | last = Lonsdale | first = Derrick | last2 = Marrs | first2=Chandler}}</ref>  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,<ref>{{Cite journal | last =Costantini | first = Antonio | last2 = Fancellu | first2 = Roberto | date = 2016 | title=An open-label pilot study with high-dose thiamine in Parkinson's disease|url=http://www.nrronline.org/text.asp?2016/11/3/406/179047|journal=Neural Regeneration Research|language=en|volume=11|issue=3|pages=406|doi=10.4103/1673-5374.179047|issn=1673-5374|pmc=PMC4828997|pmid=27127471}}</ref><ref>{{Cite journal | last =Costantini | first = Antonio | last2 = Pala |  first2 = Maria Immacolata | last3 = Grossi | first3 = Enzo | last4 = Mondonico | first4 = Stella| last5 = Cardelli | first5 = Luisa Ercoli | last6 = Jenner | first6 = Carina | last7 = Proietti | first7 = Sabrina | last8 = Colangeli | first8 = Marco | last9 = Fancellu | first9 = Roberto | date = Dec 2015 | title = Long-Term Treatment with High-Dose Thiamine in Parkinson Disease: An Open-Label Pilot Study|url=http://www.liebertpub.com/doi/10.1089/acm.2014.0353|journal=The Journal of Alternative and Complementary Medicine|language=en|volume=21|issue=12 | pages = 740–747|doi=10.1089/acm.2014.0353|issn=1075-5535}}</ref> [[multiple sclerosis]],<ref>{{Cite journal | last =Costantini | first = A. | last2 = Nappo | first2 = A. | last3 = Pala | first3=M.I. |  last4 = Zappone | first4 = A. | date = 2013-07-16 | title = High dose thiamine improves fatigue in multiple sclerosis|url=https://casereports.bmj.com/lookup/doi/10.1136/bcr-2013-009144|journal=Case Reports|language=en|volume=2013|issue=|pages=bcr2013009144–bcr2013009144|doi=10.1136/bcr-2013-009144|issn=1757-790X|pmc=PMC3736110|pmid=23861280}}</ref> [[fibromyalgia]],<ref>{{Cite journal | last =Costantini | first = A. | last2 = Pala |  first2 = M.I. |  last3 = Tundo | first3 = S. | last4 = Matteucci | first4 = P. | date = 2013-05-20 | title = High-dose thiamine improves the symptoms of fibromyalgia|url=https://casereports.bmj.com/lookup/doi/10.1136/bcr-2013-009019|journal=Case Reports|language=en|volume=2013|issue=may20 1|pages=bcr2013009019–bcr2013009019|doi=10.1136/bcr-2013-009019|issn=1757-790X|pmc=PMC3669831|pmid=23696141}}</ref> [[inflammatory bowel disease]],<ref>{{Cite journal | last =Costantini | first = Antonio | last2 = Pala |  first2 = Maria Immacolata | date = Aug 2013 | title = Thiamine and Fatigue in Inflammatory Bowel Diseases: An Open-label Pilot Study|url=http://www.liebertpub.com/doi/10.1089/acm.2011.0840|journal=The Journal of Alternative and Complementary Medicine|language=en|volume=19|issue=8 | pages = 704–708|doi=10.1089/acm.2011.0840|issn=1075-5535}}</ref> and [[migraine|cluster headaches]].<ref>{{Cite journal | last = Antonio | first = Costantini | last2 = Massimo | first2 = Tiberi | last3 = Gianpaolo | first3 = Zarletti | last4 = Immacolata | first4 = Pala Maria| last5 = Erika | first5 = Trevi | date = 2018 | title=Oral High-Dose Thiamine Improves the Symptoms of Chronic Cluster Headache|url=https://www.hindawi.com/journals/crinm/2018/3901619/|journal=Case Reports in Neurological Medicine|language=en|volume=2018|pages=1–5|doi=10.1155/2018/3901619|issn=2090-6668|pmc=PMC5932500|pmid=29850313}}</ref>  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 sex.  (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.<ref>{{Cite journal | last =Bager | first=Palle|author-link = | last2 = Hvas | first2=Christian | authorlink2 = | last3 = Rud | first3=Charlotte | author-link3 = | last4 = Dahlerup | first4 = Jens | author-link4 = | date = Oct 2020 | title = Randomised clinical trial: high-dose oral thiamine versus placebo for chronic fatigue in patients with quiescent inflammatory bowel disease.|url=https://onlinelibrary.wiley.com/doi/epdf/10.1111/apt.16166|journal=Aliment Pharmacol Ther.|volume=53|issue=1 | pages = 79–86.|doi=10.1111/apt.16166|pmc=|pmid=|access-date=2021-08-22|quote=|via=}}</ref>  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,<ref name=":0">{{Cite journal | last =Lubell | first = Jeffrey | author-link= | date = Mar 2021 | title = Letter: future studies of high-dose thiamine should consider whether its effects on fatigue are related to the inhibition of carbonic anhydrase isoenzymes|url=https://onlinelibrary.wiley.com/doi/full/10.1111/apt.16275|journal=Aliment Pharmacol Ther.|volume=53|issue= | pages = 851-852|doi=|pmc=|pmid=|access-date=2021-08-22|quote=|via=}}</ref> focuses on high-dose thiamine's property as a carbonic anhydrase inhibitor, which has been proven in vitro,<ref>{{Cite journal | last =Özdemir | first=Zafer Ömer | last2=Şentürk | first2 = Murat | last3 = Ekinci | first3 = Deniz | date = 2013-04-01 | title = Inhibition of mammalian carbonic anhydrase isoforms I, II and VI with thiamine and thiamine-like molecules|url=https://www.tandfonline.com/doi/full/10.3109/14756366.2011.637200|journal=Journal of Enzyme Inhibition and Medicinal Chemistry|language=en|volume=28|issue=2|pages=316–319|doi=10.3109/14756366.2011.637200|issn=1475-6366}}</ref> 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<ref>{{Cite journal | last = Vesela | first=A | authorlink = | last2 = Wilhelm | first2 = J | authorlink2 =  | date = 2002 | title=The role of carbon dioxide in free radical reactions of the organism.|url=https://pubmed.ncbi.nlm.nih.gov/12449430/|journal=Physiol Res.|volume=51|issue=4|pages=335–33|doi=|pmc=|pmid=12449430|access-date=|quote=|via=}}</ref>; or (d) by dampening the pro-inflammatory Th-17 pathway<ref>{{Cite journal | last = Vatsalya |  first = Vatsalya | last2 = Li | first2 = Fengyuan | last3 = Frimodig | first3 = Jane | last4 = Gala | first4 = Khushboo S. | last5 = Srivastava | first5 = Shweta | last6 = Kong | first6 = Maiying | last7 = Ramchandani | first7 = Vijay A. | last8 = Feng | first8 = Wenke | last9 = Zhang | first9 = Xiang | date = 2021-03-02 | title = Repurposing Treatment of Wernicke–Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile|url=https://www.frontiersin.org/articles/10.3389/fphar.2020.598128/full|journal=Frontiers in Pharmacology|volume=11|pages=598128|doi=10.3389/fphar.2020.598128|issn=1663-9812|pmc=PMC7960760|pmid=33737877}}</ref>, again through the Bohr effect, potentially mediated by reductions in hypoxia-inducible factor 1.<ref>{{Cite journal | last =Nutsch | first = Katherine | last2 = Hsieh | first2 = Chyi | date = Sep 2011 | title = When T Cells Run Out of Breath: The HIF-1α Story|url=https://linkinghub.elsevier.com/retrieve/pii/S0092867411009445|journal=Cell|language=en|volume=146|issue=5 | pages = 673–674|doi=10.1016/j.cell.2011.08.018}}</ref><ref name=":0" />. A more complete explanation of this hypothesis can be found here.{{Citation needed | date = 2021}}   

Studies have also examined the potential of the thiamine derivative, sulbutiamine, to reduce fatigue.<ref>{{Cite journal | last =Sevim | first = Serhan | last2 = Kaleağası | first2 = Hakan | last3 = Taşdelen | first3=Bahar | date = Aug 2017 | title = Sulbutiamine shows promising results in reducing fatigue in patients with multiple sclerosis|url=https://linkinghub.elsevier.com/retrieve/pii/S2211034817301190|journal=Multiple Sclerosis and Related Disorders|language=en|volume=16|pages=40–43|doi=10.1016/j.msard.2017.05.010}}</ref>

==Chronic fatigue syndrome==
One very small study found decreased functional status of several [[B vitamin]]s including [[Vitamin B6|pyridoxine]], [[riboflavin]] and thiamine.<ref name="vitbcfs1999" />

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]]s was reported in Health Rising in 2021.<ref>{{Cite web|url=https://www.healthrising.org/blog/2021/06/02/fibromyalgia-chronic-fatigue-syndrome-benefit-high-dose-thiamine/ | title = Nearly 2/3rds of Survey Respondents Report Large Benefits from High-Dose Thiamine (B-1) | last =Lubell | first = Jeffrey | authorlink= | date = | website = Health Rising|archive-url=|archive-date=|url-status=|access-date=2021-08-22}}</ref>  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. 

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.<ref>{{Cite journal | last =Smithline | first = Howard A | last2 = Donnino | first2 = Michael | last3 = Greenblatt | first3=David J | date = Dec 2012 | title = Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects|url=http://link.springer.com/10.1186/1472-6904-12-4|journal=BMC Clinical Pharmacology|language=en|volume=12|issue=1|pages=4|doi=10.1186/1472-6904-12-4|issn=1472-6904|pmc=PMC3293077|pmid=22305197}}</ref>

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

==Learn more==
*[http://lpi.oregonstate.edu/mic/vitamins Linus Pauling Institute Micronutrient Information Center - Thiamine]

==See also==
*[[Vitamin]]

==References==
<references>
<ref name="vitbcfs1999">{{Citation| doi = 10.1177/014107689909200405| issn = 0141-0768| volume = 92 | issue = 4| pages = 183–185| last1 = Heap | first1 = L.C. | last2 = Peters | first2 = T.J. | last3 = Wessely | first3 = S.| title = Vitamin B Status in Patients with Chronic Fatigue Syndrome| journal = Journal of the Royal Society of Medicine| access-date = 2016-11-09| date = 1999-04-01| url = http://jrs.sagepub.com/content/92/4/183 | pmid = 10450194}}</ref>
</references>

[[Category:Potential treatments]]
[[Category:Supplements]]
[[Category:B vitamins]]
[[Category:Nutrients]]