Thiamin(e): The Spark of Life

  • Derrick Lonsdale
Part of the Subcellular Biochemistry book series (SCBI, volume 56)


One of the earliest vitamins to be discovered and synthesized, thiamin was originally spelled with an “e”. The terminal “e” was dropped when it was found that it was not an amine. It is still spelled with and without the “e” depending on the text. This chapter provides a brief historical review of the association of thiamin with the ancient scourge of beriberi. It emphasizes that beriberi is the model for high calorie malnutrition because of its occurrence in predominantly white rice consuming cultures. Some of the symptomatology of this ancient scourge is described, emphasizing the difference from that seen in starvation. High calorie malnutrition, due to excessive ingestion of simple carbohydrates, is widely encountered in the U.S.A. today. Thiamin deficiency is commonly associated with this, largely because of its cofactor status in the metabolism of glucose. The biochemistry of the three phosphorylated esters of thiamin and the transporters are discussed and the pathophysiology of thiamin deficiency reviewed. The role of thiamin, and particularly its synthetic derivatives as therapeutic agents, is not fully appreciated in Western civilization and a clinical section describes some of the unusual cases described in the scientific literature and some experienced by the author. The possible role of high calorie malnutrition and related thiamin deficiency in juvenile crime is hypothesized.


Sudden Infant Death Syndrome Thiamin Deficiency White Rice Maple Syrup Urine Disease Simple Carbohydrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adamolekum B, Ndububa DA (1994) Epidemiology and clinical presentation of a seasonal ataxia in Western Nigeria. J neurol Sci 124(1):95–98Google Scholar
  2. Bannister R (ed) (1984) Autonomic failure: a textbook of clinical disorders of the autonomic nervous system, 2nd edn. Oxford University PressGoogle Scholar
  3. Barker JN, Jordan F (1982) Phrenic thiamin and neuropathy in sudden infant deaths. In: Sable HZ, Gubler CJ (eds) Thiamin: twenty years of progress. Ann N Y Acad Sci 378: 449–452Google Scholar
  4. Beltramo E, Berrone E, Buttiglieri S, Porta M (2004) Thiamine and benfotiamine prevent increased apoptaosis in endothelial cells and pericytes cultured in high glucose. Diabetes Metab Res Rev 20(4):330–336PubMedGoogle Scholar
  5. Bettendorff L, Michel-Cahay C, Grandfils C, DeRycker C, Schoffeniels E (1987) Thiamine triphosphate and membrane-associated thiamine phosphatases in the electric organ of Electophorus electricus. J Neurochem 49:495–502PubMedGoogle Scholar
  6. Bettendorff L, Kolb HA, Schoffeniels E (1993) Thiamine triphosphate activates anion channels of large unit conduction in neuroblastoma cells. J Membr Biol 136:281–288PubMedGoogle Scholar
  7. Bettendorff L, Hennuy B, De Cherek A, Wins P (1994) Chloride permeability of rat brain vesicles correlates with thiamine trophosphate content. Brain Res 652:157–160PubMedGoogle Scholar
  8. Bhuvaneswaran C, Sreenivaran A (1962) Problems of thiamine deficiency states and their amelioration. Ann N Y Acad Sci 98:576–601PubMedGoogle Scholar
  9. Bitsch R, Wolf M, Moller J et al (1991) Bioavailability assessment of the lipophilic benfotiamine as compared to a water-soluble thiamine derivative. Ann Nutr Metab 35:292–296PubMedGoogle Scholar
  10. Blass J (1972) Abnormalities in pyruvate dehydrogenase and neurologic function. Intern J Neruosci 4:65–69Google Scholar
  11. Blass JP, Gibson GE (1977) Abnormality of a thiamine requiring enzyme in patients with Wernicke-Korsakoff syndrome. N Engl J Med 297:1367–1370PubMedGoogle Scholar
  12. Blass JP, Gleason P, Brush D, DiPonte P, Thaler H (1988) Thiamine and Alzheimer’s disease. Arch Neurol 45:833–835PubMedGoogle Scholar
  13. Boni L, Kieckens L, Hendricx A (1980) An evaluation of a modified erythrocyte transketolase assay for assessing thiamine nutritional adequacy. J Nutr Sci Vitaminol 26:507–514PubMedGoogle Scholar
  14. Brin M (1964) The antithiamine effects of amprolium in rats on tissue transketolase activity. Toxicol Appl Pharmacol 6:454–458PubMedGoogle Scholar
  15. Caddell JL (1972) Magnesium deprivation in sudden unexpected infant death. Lancet ii258–262Google Scholar
  16. Cooper JR, Pincus JH (1979) The role of thiamine in nervous tissue. Neurochem Res 4:223–239PubMedGoogle Scholar
  17. Cooper JR, Itokawa Y, Pincus JH (1969) Thiamine triphosphate deficiency in subacute necrotizing encephalomyelopathy. Science 164:72–73Google Scholar
  18. Cooper JR, Pincus JH, Itokawa Y, Piros K (1970) Experiences with phosphoribosyl transferase inhibition in subacute necrotizing encephalomyelopathy. N Engl J Med 283:793–795PubMedGoogle Scholar
  19. Dancis J, Hutzler J, Rokkones T (1967) Intermittent branched chain ketonuria: Variant of maple-syrup-urine disease. New Engl J Med 276:84–89PubMedGoogle Scholar
  20. Djoenaidi W, Notermans SL (1990) Thiamine tetrahydrofurfuryl disulfide in nutritional polyneuropathy. Eur Arch Psychiatry Neurol Sci 239:218–220PubMedGoogle Scholar
  21. Djoenaidi W, Notermans SL, Dunda G (1992) Beriberi caardiomyopathy Eur J Clin Nutr 46:227–234PubMedGoogle Scholar
  22. Duran M, Tielens AGM, Wadman SK et al (1978) Effects of thiamine in a patient with a variant form of branched-chain ketoaciduria. Acta Paediatr Scand 67:367–372PubMedGoogle Scholar
  23. Dyckner T, Elk B, Nyhlin H, Wester PO (1985) Aggravation of thiamine deficiency by magnesium depletion. A case report. Acta Scand 218:129–131Google Scholar
  24. Edwin EE, Jackman R (1970) Thiaminase I in the development of cerebrocortical necrosis in sheep and cattle. Nature 228(5273):772–774PubMedGoogle Scholar
  25. Eisinger J, Bagneres D, Arroyo P, Plantamura A, Ayavou T (1994) Effect of magnesium, high energy phophates, piracetam and thiamin on erythrocyte transketolase. Magnes Res 7:59–61PubMedGoogle Scholar
  26. Elmadfa I, Majchrzak D, Rust P, Genser D (2001) The thiamine status of adult humans depend on carbohydrate intake. Int J Vitam Nutr Res 71:217–221PubMedGoogle Scholar
  27. Elsas LJ, Danner DJ (1982) The role of thiamin in maple syrup urine disease. In: Sable LJ, Gubler CJ (eds) Thiamin: twenty years of progress. Ann N Y Acad Sci 378: 404–420Google Scholar
  28. Fehily L (1944) Human milk intoxication due to B1 avitaminosis. Br Med J 2:590–592PubMedGoogle Scholar
  29. Frank T, Bitsch R, Malwaki J, Stein G (1999) Alteration of thiamine phramacokinetics by end-stage renal disease (ESRD). Int J Clin Pharmacol Ther 37:449–455PubMedGoogle Scholar
  30. Fujita A (1954) Thiaminase. In: Nord FF (ed) Advances in enzymology, vol 15—. Interscience Publishers, pp 389–421Google Scholar
  31. Fujita T, Suzuoki Z (1973a) Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. I Microsomal S-transmethylase. J Biochem 74:717–722PubMedGoogle Scholar
  32. Fujita T, Suzuoki Z (1973b) Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. III Oxidative cleavage of the tetrahydrofuran moiety. J Biochem 74:733–738PubMedGoogle Scholar
  33. Fujita T, Suzuoki Z, Kozuka S (1973a) Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. II Sulfide and sulfoxide oxygenases in microsomes. J Biochem 74:723–732PubMedGoogle Scholar
  34. Fujita T, Teraoka A, Suzuoki Z (1973b) Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. IV Induction of microsomal S-transmethylase and sulfide and sulfoxide oxygenases in the drug-treated rat. J Biochem 74:739–745PubMedGoogle Scholar
  35. Fujiwara M (1965) Absorption, excretion and fate of thiamine and its derivatives in [the] human body. In: Shimazono N, Katsura E (eds) Thiamine and Beriberi. Igaku Shoin Ltd, Tokyo, pp 179–213Google Scholar
  36. Ganapathy V, Smith SB, Prasad PD (2004) SLC19: the folate/thiamine transporter family. Pflugers Arch 447:641–646PubMedGoogle Scholar
  37. Gibson GE, Barclay L, Blass J (1982) The role of the cholinergic system in thiamin deficiency. In: Sable HZ, Gubler CJ (eds) Thiamin: twenty years of progress. Ann N Y Acad Sci 378: 382–403Google Scholar
  38. Gibson GE, Zhang H (2002) Interactions of oxidative stress with thiamine homeostasis promote neurodegeneration. Neurochem Int 40:493–504PubMedGoogle Scholar
  39. Gray GE (1987) Crime and diet: Is there a relationship? Wld Rev Nutr Diet 49:66–86Google Scholar
  40. Harada H, Rikimaru F, Mori T, Tanaka ME et al (2002) Electroencephalographic changes during intravenous olfactory stimulation in humans. Clin Electroencephalogr 33:189–192PubMedGoogle Scholar
  41. Haupt E, Ledermann H, Kopcke W (2005) Benfotiamine in the treatment of diabetic polyneuropathy—a three–week randomized, controlled pilot study (BEDIP study) Int J Clin Pharmacol Ther 2005;43:71–77. Erratum in: Int J Clin Pharmacol Ther 2005;43:304Google Scholar
  42. Henderson GI, Schenker S (1975) Reversible impairment of cerebral DNA synthesis in thiamine deficiency. J Lab Clin Med 86:77–90PubMedGoogle Scholar
  43. Inouye K, Katsura E (1965) Etiology and pathology of beriberi. In: Thiamine and Beriberi. Igaku Shoin Ltd., Tokyo, pp 1–28Google Scholar
  44. Iwata H, Nishikawa T, Fujimoto S (1969a) Monoamine oxidase activities in tissues of thiamine-deficient rats. J Pharm Pharmac 21:237–240Google Scholar
  45. Iwata H, Watanabe K, Nishikawa T, Ohashi M (1969b) Effects of drugs on behavior, heart rate and catecholamine levels in thiamine-deficient rats. Eur J Pharmacol 6:83–89PubMedGoogle Scholar
  46. Iwata H, Yabushita Y, Doi T, Matsuda T (1985) Synthesis of thiamine triphosphate in rat brain in vivo. Neurochem Res 10:779–787PubMedGoogle Scholar
  47. Jansen BCT, Donath WF (1926) On the isolation of the anti-beriberi vitamin. Proc I Acad Wei Amsterdam 29:1390Google Scholar
  48. Jeffrey HE, McCleary BV, Hensley WJ, Read DJC (1985) Thiamine deficiency- a neglected problem of infants and mothers- possible relationship to sudden infant death syndrome. Aust NZ J Obst Gynaecol 25:198–202Google Scholar
  49. Jeyasingham MD, Pratt O, Burns A, Shaw GK, Thompson A, Marsh A (1987) The activation of red blood cell transketolase in groups of patients especially at risk from thiamin deficiency. Psych Med 117:311–318Google Scholar
  50. Kikuchi S, Nishikawa K, Suzuoki Z (1970) The metabolism of thiamine thetrhydrofurfuryl disulfide in the rat, rabbit and man. Eur J Pharmacol 9:367–373PubMedGoogle Scholar
  51. Kimura M, Itokawa Y (1977) Effects of calcium and magnesium deficiency on thiamine distribution in rat brain and liver. J Neurochem 28:389–393PubMedGoogle Scholar
  52. Lagarde WH, Underwood LE, Moats-Staats BM, Calikoglu AS (2004) Novel mutation in the SLC19A2 gene in an African-American female with thiamine-responsive megaloblastic anemia syndrome. Am J Med Genet 125:299–305Google Scholar
  53. Lesch M, Nyhan WL (1964) A familial disorder of uric acid metabolism and central nervous system function. Am J Med 36:561–570PubMedGoogle Scholar
  54. Loew FM (1974) Possible animal model of subacute necrotizing (Leigh’s) encephalomyelopathy J Pediat 85:876–877PubMedGoogle Scholar
  55. Lonsdale D (1975) Thiamine metabolism in disease. Crit Rev Lab Sci 5:289–313Google Scholar
  56. Lonsdale D (1977) Treatment of threatened SIDS with megadose thiamine hydrochloride. Pediat Res 11:379 (Abstr)Google Scholar
  57. Lonsdale D (1978) Wernicke’s encephalopathy and hyperalimentation. JAMA 239:1133. (Letter to the editor)PubMedGoogle Scholar
  58. Lonsdale D (1980) Recurrent febrile lymphadenopathy treated with large doses of vitamin B1: Report of two cases. Dev Pharmacol Ther 1:254–264PubMedGoogle Scholar
  59. Lonsdale D (1981) The syndrome of functional dysautonomia. Med Hypoth 7:495–502Google Scholar
  60. Lonsdale D (1982) Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/J2 mice. Dev Pharmacol Ther 4:28–36PubMedGoogle Scholar
  61. Lonsdale D (1987a) A nutritionist’s guide to the clinical use of vitamin B1. Life Sciences Press, Tacoma, pp. 5–12Google Scholar
  62. Lonsdale D (1987b) Biochemical studies in functional dysautonomia. In: A nutritionist’s guide to the clinical use of vitamin B1. Life Sciences Press, Tacoma, WA, pp. 78–115Google Scholar
  63. Lonsdale D (1990a) Hypothesis and case reports: possible thiamin deficiency. J Am Coll Nutr 9:13–17PubMedGoogle Scholar
  64. Lonsdale D (1990b) Asymmetric functional dysautonomia. J Nutr Med 1:59–61Google Scholar
  65. Lonsdale D (1990c) Thiamine deficiency and sudden deaths. Lancet ii:376Google Scholar
  66. Lonsdale D (1992a) Criminal behavior and nutrition. J Adv Med 5(2):494–504Google Scholar
  67. Lonsdale D (1992b) Criminal behavior and nutrition. J Adv Med 5:115–123Google Scholar
  68. Lonsdale D (1994a) Crime and violence: A hypothetical explanation of its relationship with high calorie malnutrition. J Adv Med 7(3):171–180Google Scholar
  69. Lonsdale D (1994b) The three circles of health. In: Why I left orthodox medicine. Hampton Roads Publishing Company, Charlottesville, pp 189–207Google Scholar
  70. Lonsdale D (2001a) Nutritional therapy in children with functional disorders of activity, behavior, attention and learning. Clin Pract Altern Med 2:196–203Google Scholar
  71. Lonsdale D (2001b) Sudden infant death syndrome requires genetic predisposition, some form of stress and marginal malnutrition. Med Hypoth 57:382–386Google Scholar
  72. Lonsdale D (2006b) A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. eCAM 3(1):49–59PubMedGoogle Scholar
  73. Lonsdale D (2006c) Three case reports to illustrate clinical applications in the use of transketolase. eCAM 4(2):247–250Google Scholar
  74. Lonsdale D, Kissling CD (1987) Clinical trials with thiamine tetrahydrofurfuryl disulfide in Down’s syndrome. J Orthomolecular Med 1:169–175Google Scholar
  75. Lonsdale D, Mercer RD (1972) Primary hypoventilation syndrome. Lancet ii:487 (Letter to the editor)Google Scholar
  76. Lonsdale D, Price JW (1973) Pyruvic aciduria in the detection of thiamine responsive encephalopathy. Cleve Clin Quart 40:79–88Google Scholar
  77. Lonsdale D, Shamberger RJ (1980) Red cell transketolase as an indicator of nutritional deficiency. Am J Clinc Nutr 33:205–211Google Scholar
  78. Lonsdale D, Faulkner WR, Price JW, Smeby RR (1969) Intermittent cerebellar ataxia associated with hyperpypruvic academia, hyperalaninemia, and hyperalaninuria. Pediatrics 43:1025–1034PubMedGoogle Scholar
  79. Lonsdale D, Nodar RH, Orlowski JP (1979) The effects of thiamine on abnormal brainstem auditory evoked potentials. Cleve Clin Quart 46:83–88Google Scholar
  80. Lonsdale D, Nodar RH, Orlowski JP (1982) Brainstem dysfunction in infants reaponsive to thiamine disulfide; preliminary studies in four patients. Clin EEG 13:82–88Google Scholar
  81. Lonsdale D, Shamberger RJ, Audhya T (2002) Treatment of autistic spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study. Neuroendocrinol Lett 23:303–308PubMedGoogle Scholar
  82. Lorber A, Gazit A Z, Khoury A, Schwartz Y, Mandel H (2003) Cardiac manifestations in thiamine-responsive megaloblastic anemia syndrome. Pediatr Cardiol 24:476–481PubMedGoogle Scholar
  83. Makarchikov AE, Lakaye B, Gulyai IE, Czerniecki J, Coumans B, Wins P et al. (2003) Thiamine triphosphatase and thiamine triphophatase activities: from bacteria to mammals. Cell Mol Life Sci 60:1477–1488PubMedGoogle Scholar
  84. Markannen T, Kalliomaki JL (1966) Transketolase activity of blood cells in various clinical conditions. Am J Med Sci 252:564–569Google Scholar
  85. Markson LM, Edwin EE, Lewis G, Richardson C (1974) The production of cerebrocortical necrosis in ruminant calves by the intraruminal administration of amprolium. Br Vet J 130:9–16PubMedGoogle Scholar
  86. Mastrogiacoma P, Bettendorff L, Grisar T, Kish SJ (1996) Brain thiamine, its phosphate esters and its metabolizing enzymes in Alzheimer’s disease. Ann Neurol 39:585–591PubMedGoogle Scholar
  87. Matsui K, Hakahara H, Watanabe J, Tamatsu H, Nakayawa M et al (1985) Inhibition by thiamine tetrahydrofurfuryl disulfide (TTFD) of the arachidonic acid cascade-line activation as evidenced in the heart-lung preparation of the dog. Jpn J Pharmacol 39:375–379PubMedGoogle Scholar
  88. McCandless DW (1982) Energy metabolism in the lateral vestibular nucleus in pyrithiamin-induced thiamin deficiency. In: Sable HZ, Guhbler CJ (eds) Thiamin: twenty years of progress. Ann N Y Acad Sci 378: 355–364Google Scholar
  89. McIntyre N, Stanley NN (1971) Cardiac beriberi: two modes of presentation. Br Med J 3:567–569PubMedGoogle Scholar
  90. Meador KJ, Loring D, Nichols M, Zamrini E, Rivner M, Posas H et al (1993a) Preliminary findings of high dose thiamine in dementia of Alzheimer’s type. J Geriatr Psychiatry Neurol 6:222–229PubMedGoogle Scholar
  91. Meador KJ, Nichols ME, Franke P, Durkin MW, Oberzin RL, Moore LE et al (1993b) Evidence for a central cholinergic effect of high dose thiamin. Ann Neurol 34:724–726PubMedGoogle Scholar
  92. Mimori Y, Katsuoka H, Nakamura S (1996) Thiamine therapy in Alzheimer’s disease. Metab Brain Dis 11(1):89–94PubMedGoogle Scholar
  93. Minz B (1938) Sur la liberation de la vitamin par le tronc isole de nerf pheumogastrique soumis a la excitation electrique. C.R. Soc Biol (Paris) 127:1251–1253Google Scholar
  94. Murata K (1965) Thiaminase. In: Shimazono N, Katsura E (eds) Beriberi and thiamine. Igaku Shoin Ltd., Tokyo, pp 220–254Google Scholar
  95. Nabokina SM, Said HM (2004) Characterization of the 5′-regulating region of the human thiamin transporter SLC19A3: In vitro and in vivo studies. Am J Physiol Gastrointest Liver Physiol 287:G822–G829PubMedGoogle Scholar
  96. Nishimune T, Watanabl Y, Okazaki H, Akai H (2000) Thiamin is decomposed due to Anaphe spp. Entomophagy in seasonal ataxia patients in Nigeria. J Nutr 130:1625–1628PubMedGoogle Scholar
  97. Oishi K, Barchi M, Au AC, Gelb BD, Diaz GA (2004) Male infertility due to germ cell apoptosis in mice lacking the thiamin carrier Tht1. A new insight into the critical role of thiamin in spermatogenesis. Dev Biol 266:299–309PubMedGoogle Scholar
  98. Ozdemir MA, Alcakus M, Kuroglu, Gunes T, Torun YA (2002) TRMA syndrome (thiamine-responsive megaloblastic anemia): a case report and review of the literature. Pediatr Diab 3:205–209Google Scholar
  99. Pang JA, Yardumian A, Davies R, Patterson DL (1986) Shoshin beriberi an underdiagnosed condition? Intensive Care Med 12(5):380–382PubMedGoogle Scholar
  100. Peters RA (1936) The biochemical lesion in vitamin B1 deficiency. Lancet 1:1162–1165Google Scholar
  101. Platt BS (1967) Thiamine deficiency in human beriberi and in Wernicke’s encephalopathy. In: Wolstenholme GEW, O’Connor M (eds) Thiamine deficiency. Little Brown and Company, Boston, pp 135–143Google Scholar
  102. Rogers LE, Porter FS, Sidbury JB (1969) Thiamine-responsive megaloblastic anemia. Pediat 74:494–504Google Scholar
  103. Sable HZ, Gubler CJ (eds) (1982) Thiamin: twenty years of progress. Ann NY Acad Sci 378:355–364Google Scholar
  104. Schauss A (1981) Diet, crime and delinquency. Berkeley, CA, pp 1–108Google Scholar
  105. Scriver CR, Mackenzie S, Clow CL, Delvin E (1971) Thiamine-responsive maple-syrup urine disease. Lancet i:310–312Google Scholar
  106. Seligman H, Halkin H, Rauchfleisch S et al (1991) Thiamine deficiency in patients with congestive heart failure receiving long-term furosemide therapy: a pilot study. Am J Med 91:151–155Google Scholar
  107. Shreeve JE, Edwin EE (1974) Thiaminase-producing strains of Cl. Sporogenes associated with outbreaks of cerebrocortical necrosis. Vet Rec 94(15):330PubMedGoogle Scholar
  108. Stepuro AL, Piletskaya TO, Stepura II (2005) Role of thiamine thiol forms in nitric oxide metabolism. Biochemistry (Mosc) 70:339–349Google Scholar
  109. Thornalley PJ (2003) Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes 57:2110–2120Google Scholar
  110. Wells DG, Baylis EM, Holoway L, Marks V (1968) Erythrocyte-transketolase activity in megaloblastic anaemia. Lancet ii:543–545Google Scholar
  111. Williams RR (1938) Chemistry of thiamine (Vitamin B1). JAMA 110:727–731Google Scholar
  112. Williams RD, Mason HL, Marschelle HP, Russell MW (1943) Induced thiamine (Vitamin B1) deficiency in man. Arch Int Med 71:38–53Google Scholar
  113. Yui Y, Fujiwara H, Mitsui H et al (1978) Furosemide-induced thiamine deficiency (abstract). Jpn Circ J 4:744Google Scholar
  114. Zbinden G (1962) Therapeutic use of vitamin B1 in diseases other than beriberi. Ann NY Acad Sci 98:550–561PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Preventive Medicine GroupWestlakeUSA

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