Table 1: Symptoms described by a 14-year-old boy with eosinophilic esophagitis
Derrick Lonsdale*Associate Emeritus, Cleveland Clinic Foundation, Cleveland, Ohio, USA
*Corresponding author: Derrick Lonsdale, Associate Emeritus, Cleveland Clinic Foundation, Cleveland, Ohio, USA, E-mail: email@example.com
Eosinophilic esophagitis is an inflammatory condition, causing dysphagia, food impaction and chest pain. A minimum of 15 eosinophils per high power field by esophageal biopsy is necessary for diagnosis. It has become an increasingly important cause of gastrointestinal morbidity in the past two decades. A 14 year old boy had received a diagnosis of eosinophilic esophagitis elsewhere at the age of 8 years. His medical history had been thought for many years to be psychosomatic until endoscopy was performed. The only other positive laboratory study was eosinophilia. In spite of conventional therapy, none of which improved overall symptoms, esophagitis persisted and he had failed to gain weight and stature. Physical examination revealed many indications of autonomic dysfunction and an erythrocyte transketolase test indicated abnormal thiamine homeostasis. Treatment was started with intravenous infusions of water-soluble vitamins that included thiamine hydrochloride (THCL). Because the transketolase test became worse, THCL was replaced with thiamine tetrahydrofurfuryl disulfide (TTFD), with consequent improvement in transketolase and symptomatic response. There was a family history of alcoholism and the patient was addicted to sugar, suggesting a genetic risk to explain the abnormal thiamine homeostasis. Beriberi causes dysautonomia in its early stages. Inflammation is now known to be suppressed reflexly through the vagus nerve, itself dependent on acetylcholine. Abnormal motility of the esophagus has been reported in eosinophilic esophagitis. Failure of THCL to improve transketolase activity suggested a genetic failure in a thiamine transporter and its consequent correction with TTFD that does not require the thiamine transport system.
Eosinophilic; Esophagitis; Inflammation; Thiamin homeostasis
Eosinophilic esophagitis (EoE) is by far the most common form of eosinophilic gastrointestinal disease. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammations, triggered often by food allergens. It is often poorly responsive to therapy and there is no commonly accepted long-term treatment . It represents the most recent form of food allergy, and its control by avoiding offending foods has increasingly appeared as a therapeutic alternative to achieve and maintain remission . In a town of over 700,000 inhabitants, a study showed a rapid increase of EOE in 10 years . EoE has been reported with mediator complex subunit 12 (MED12) mutations . Of 793 patients with EoE, 72% were male . Of 173 patients with esophageal food bolus impaction, 27% were EoE . Both spinal and vagal afferents of the esophagus appear to contribute to painful sensations  and its physiology is important in its motility . The esophagus is dependent on acetylcholine for its neurological function and esophageal motor disorders have been demonstrated in EoE .
A 14 year old boy had received a diagnosis of eosinophilic esophagitis elsewhere at the age of 8 years. His history began in infancy with recurrent ear infections and asthma. His many symptoms (Table 1), thought originally to be psychosomatic, confused the diagnosis until endoscopy was performed. Many laboratory studies had been consistently negative with the exception of eosinophilia and persistence of the esophageal pathology. Conventional treatments had no effect on symptomology. He had failed to gain weight and stature. Physical examination revealed severe hyperalgesia to light touch of the abdomen. Heart auscultation revealed a click suggestive of mitral valve prolapse. Patellar deep tendon reflexes were non responsive, even with the Jandrassic maneuver. Light stroking of the inner side of thigh and leg resulted in a very slow appearance of transient white dermatographia. Laboratory studies are shown in (Table 2). He was treated first with a course of intravenous infusions of watersoluble vitamins that included thiamine hydrochloride (THCl) (Table 3). Because of increasing abnormality of erythrocyte transketolase, thiamine tetrahydrofurfuryl disulfide (TTFD) was substituted for THCL with consequent improvement in transketolase and symptomology. Body weight at the beginning of treatment was 105 pounds, placing him in the 25th percentile. After one year of treatment his weight had increased to 122 pounds, placing him in the 50th percentile. His stature increased in the same time period from 64.5 inches to 68.5 inches, raising it from the 50th to the 75th percentile.
This boy was 18 years of age at the time of writing. Abdominal pain was variable and associated with visible contraction of abdominal muscles. Headaches, nausea, joint pain and fatigue appeared to be associated with food ingestion. Abdominal pain and need to urinate occurred spontaneously at night.
Thiamine Deficiency (TD) leads to the development of impaired energy metabolism and cerebral vulnerability . It is only relatively recently that inherited defects in thiamine uptake, activation and the attachment of the active cofactor to target enzymes have been described . Genetic variation in the SLC19A3 thiamine transporter may make a modest contribution toward genetic susceptibility to alcoholic dependence syndrome , possibly of importance in the family history of this patient. TD causes oxidative stress in brain mitochondria . In a patient with atrophic beriberi there were 37 mutations in the SLC family of thiamine transporters . TD in rats reduced acetylcholine-mediated relaxation and increased phenylephrine-mediated vasoconstriction in the aortas containing functional endothelium . TD induces HIF1-alphamediated gene expression similar to that observed in hypoxic stress . Deleting this factor in mice caused intensified hyperalgesia, suggesting its duality in pain regulation  and its possible bearing on the hyperalgesia/ allodynia expressed by the patient. Sepsis in critically ill patients may be associated with TD and experimental TD resulted in oxidative stress and inflammatory response changes in mice . In human tissues the total thiamine content is lower than in other animal species. The high sensitivity of humans to thiamine deficiency may be linked to this .
Table 2: Laboratory results from a boy with eosinophilic esophagitis
Table 3: Water soluble intravenous vitamin infusion given to a boy with eosinophilic esophagitis
The Mayo Clinic has indicated that the best way of measuring thiamine deficiency is an assay of blood thiamine. Like magnesium, this may be misleading since it is its intracellular content that counts. Measuring the function of the thiamine dependent enzyme, erythrocyte transketolase activity before (TKA) and after the addition of thiamine pyrophosphate (TPPE) clearly indicates thiamine deficiency. The TKA increases within the normal range as the TPPE decreases after the administration of thiamine .
Peters was the first to recognize the relationship between thiamine and glucose. The pathology of the nervous system in thiamine deficient pigeons was similar to that in beriberi and Peters compared the respiration of TD pigeon brain cells with those that were thiamine sufficient. No difference occurred until glucose was added to the preparation when it became obvious that the production of carbon dioxide began immediately in thiamine sufficient cells whereas it did not in TD cells. Peters called this the catatorulin effect , thus emphasizing that ingestion of excessive simple carbohydrates, referred to as high calorie malnutrition, automatically increases the need for this vitamin . Thiamine pyrophosphate is a cofactor for 2-hydroxyacyl CoA lyase (HACL1) in the peroxisome, making alpha oxidation dependent on thiamine for fat metabolism, [23-25].
Action potentials originating in the vagus nerve regulate T cells that in turn produce acetylcholine, required to control innate immune responses . Cholinergic neurons require acetyl-CoA, derived from pyruvate dehydrogenase, in order to synthesize acetylcholine , vital to the function of the esophagus . It is hypothesized that TD resulted in deficiency of acetylcholine and failure of vagal suppression of inflammation as well as affecting esophageal motility in this patient.
Dysautonomia does not produce unique symptoms. It is the set of symptoms, taken together, that suggests that a dysautonomic state is present. Familial Dysautonomia (FD) was described in 1949, but Riley and Moore later went on to notice other dysautonomic syndromes [28,29]. Considering the critical dependence of the brain on glucose, it is capable of controlling its metabolism through the neuroendocrine axis. As a result, our understanding of diseases should be expanded to consideration of neural inputs in a concept of the pathophysiological process . This patient exhibited a number of clinical phenomena that indicated autonomic dysfunction. Examination revealed the unmistakable mid systolic click of Mitral Valve Prolapse (MVP), associated with dysautonomia in 1979 . Ninety-four patients were identified with MVP and 59 of them had low concentrations of red cell magnesium in erythrocytes . Thiamin and magnesium work together as cofactors for thiamin dependent enzymes. Inhalation of carbon dioxide can induce in humans an emotion closely replicating spontaneous panic attacks , one of the symptoms recorded in the history of this patient. Since hypoxia results in sympathetic overdrive in animal studies  and TD causes oxidative imbalance described as pseudo-hypoxia, it is hypothesized that panic attacks are fragmented fight-or-flight reflexes, initiated by TD in this patient. His history of ADD/OCD, that had caused some diagnostic confusion before the diagnosis of EoE showed some clinical improvement as a result of his vitamin treatment. Oxidative stress has been reported in ADD/ADHD) . In his early history, this patient had recurrent otitis media, a frequent disorder attributed to oxidative stress . He also had experienced recurrent asthma, a disease that occurred in the history of a child with intermittent cerebellar ataxia due to thiamin dependency . Of 1,180 patients with EoE, 160 (14%) were suspected of having aeroallergen-associated triggers by history and 32 (20%) had biopsy confirmation of this. Most of them were boys (84%). All had a history or examination consistent with allergic rhinitis and 75% had a history of asthma . Several pathogenic mechanisms related to the nervous system have been reported in non allergic rhinitis, including dysautonomia . Riley noted that failure of general body growth in Familial Dysautonomia appears to be a regular feature despite normal growth hormone . Perhaps the delay in growth would not have been noticed in this patient if he had not had a phenomenal growth acceleration of 4 inches in height and a weight increase of 17 pounds in one year of treatment. The higher percentiles for both showed that this was an unusual acceleration of growth. It is unknown whether the mechanism for growth failure in FD is directly related to the genetic cause of the disease or because of the resulting dysautonomia. Since the dysautonomia in this patient appears to have been acquired in relationship to thiamine metabolism, it suggests that growth failure was related to the dysautonomia.
The role of thiamine derivatives
If TD was the primary biochemical lesion in this patient and its clinical effects started in infancy, an explanation is needed for the adverse response of erythrocyte transketolase to the administration of thiamine hydrochloride. The mechanism is unknown, but the clinical and laboratory response to thiamin tetrahydrofurfuryl disulfide (TTFD) suggests a genetically determined thiamin transporter problem. TTFD, an open ring form of thiamin, is reduced at the cell membrane non enzymatically. The thiazolium ring closes and an intact form of thiamin is introduced into the cell . The early symptoms of TD are due to dysautonomia, frequently diagnosed as psychosomatic and easily reversible at this stage. It has been hypothesized that if these symptoms are not recognized and the biochemical lesion is allowed to continue because of failure to correct the TD, unpredictable complications may follow . The role of genetic risk is expanding: for example, deficiency or dependency of thiamine pyrophosphate can cause a defect in pyruvic dehydrogenase , the dehydrogenase of branched-chain amino acids , or thiamine pyrophosphate kinase , although the clinical effects vary. All of these genetically determined conditions are treatable with pharmacologic doses of thiamine. Therefore the phenol typical expression of the disease is much less important than spotting the biochemical lesion. Due to genetic defects of this type, there may be many individuals who require higher amounts of thiamine, not typically provided by the diet. Thiamine precursor drugs can achieve these high blood levels and result in increased concentrations in the central nervous system [44,45]. An experiment in DBA/J2 mice suggested also that TTFD had a cholinergic effect . An S-alkyl derivative of thiamine (benfotiamine) has had a beneficial effect on peripheral nerve function and inflammatory markers in type I diabetes  and significantly decreased pro-inflammatory mediators in liposaccharide-stimulated murine BV-2 microglia . It has been shown, however, that this derivative is practically insoluble in water, organic solvents or oil, making it unsuitable for intravenous use. When solubilized in hydroxypropyl-beta-cyclodextrxin and given to mice, thiamine levels rapidly increased in blood and liver but there was no significant increase observed in the brain. These investigators proposed that benfotiamine only penetrates the cells after dephosphorylation by intestinal alkaline phosphatases, entering the bloodstream as S-benzoylthiamine that is converted to thiamine in erythrocytes and in the liver. This derivative should therefore be differentiated from true lipid-soluble thiamine disulfide derivatives and used appropriately . It has been shown that TTFD inhibits the arachidonic acid cascade-line activation that would make it potentially more suitable for brain inflammation . Thiamine pyrophosphate prevented cisplatin-associated oxidative stress, whereas thiamine did not prevent this . TTFD rapidly increased thiamine activity in whole blood, erythrocytes, CSF and urine in normal and thiamine-deficient subjects. Such repletion was equal to that produced by parenteral, water-soluble thiamine hydrochloride or thiamine pyrophosphate , suggesting that this derivative might be useful in the correction of TD in the peroxisome where thiamine pyrophosphate is the cofactor required . It is very unlikely that thiamine deficiency or abnormal homeostasis is the ultimate biochemical lesion in causing EoE. For example vitamin D deficiency has been associated with increased risk for severe asthma, challenge proven food allergy, severe atopic dermatitis and EoE . It is hypothesized therefore that the biochemical lesion, whether it be genetically determined, nutritional in origin, or a combination of the two, represents the etiology for EoE that might be applicable to the etiology of other diseases.
Evidence has been presented that a single patient with EoE had abnormal thiamine metabolism as the underlying ultimate etiology. It has been hypothesized that acetylcholine deficiency, resulting from inefficient citric acid cycle function, interfered with the motility of the esophagus and failed to suppress the inflammatory reaction arising from food allergens. Since the vagus nerve supplies the intestine, it might explain the incidence of eosinophilic enteritis as well as esophagitis. The incidence of TD related EoE might be differentiated from other cases by measuring the activity of erythrocyte transketolase (TKA) and the effect on this enzyme by the addition of thiamin pyrophosphate (TPPE).
- Cianferoni A, Spergel JM (2015) Eosinophilic Esophagitis and Gastroenteritis. Curr Allergy Asthma Rep 15: 558. [Ref.]
- Lucendo AJ (2015) Meta-Analysis-Based Guidance for Dietary Management in Eosinophilic Esophagitis. Curr Gastroenterol Rep 17: 464. [Ref.]
- Giriens B, Yan P, Safroneeva E, Zwahlen M, Reinhard A, et al. (2015) Escalating Incidence of Eosinophilic Esophagitis in Canton of Vaud, Switzerland, 1993 to 2013: a population-based study. Allergy 70: 1633-1639. [Ref.]
- Langley KG, Brown J, Gerber RJ, Fox J, Friez MJ, et al. (2015) Beyond Ohdo syndrome: a familial missense mutation broadens the MED12 spectrum. Am J Genet A 167: 3180-3185. [Ref.]
- Moawad FJ, Dellon ES, Achem SR, Ljuldjuraj T, Green DJ, et al. (2015) Effects of Race and Sex on Features of Eosinophilic Esophagitis. Clin Gastro Hepatol 14: 23-30. [Ref.]
- Sengupta N, Tapper EB, Corban C, Sommers T, Leffler DA, et al. (2015) The clinical predictors of etiology and complications among 173 patients presenting to the Emergency Department with esophageal food bolus impaction from 2004-2014. Aliment Pharmacol Ther 42: 91-98. [Ref.]
- Neuhuber WL, Raab M, Berthoud HR, Worl J (2006) innervation of the mammalian esophagus. Adv Anat Embryol Cell Biol 185: 1-73. [Ref.]
- Goyal OK, Chauhury A (2008) Physiology of normal esophageal motility. J Clin Gastroenterol 42: 610-619. [Ref.]
- Santander C, Chavarria Herbozo CM, Becerro Gonzalez I, Burgos Santamaria D (2015) Impaired esophageal motor function in eosinophilic esophagitis Rev Esp Enferm Dig 107. [Ref.]
- Abdou E, Hazell AS (2015) Thiamine deficiency: an update of pathophysiologic mechanisms and future therapeutic considerations. Neurochem Res 40: 353-361. [Ref.]
- Brown G (2014) Defects of thiamine transport and metabolism. J Inherit Metab Dis 37: 577-585. [Ref.]
- Quadri G, McQuillin A, Guerrini I, Thomson AD, Cherian R, et al. (2014) Evidence for genetic susceptibility to the alcohol dependence syndrome from the thiamine transporter 2 gene solute carrier SLC19A3. Psychiatr Genet 24: 122-123. [Ref.]
- Sharma A, Bist R, Bubber P (2013) Thiamine deficiency induces oxidative stress in brain mitochondria of Mus musculus. J Physiol Biochem 69: 539-546. [Ref.]
- Bravata V, Minafra L, Callari G, Gelfi C, Edoardo Grimaldi LM (2014) Analysis of thiamine transporter genes in sporadic beriberi. Nutrition 30: 485-488. [Ref.]
- Gioda CR, Capettini LS, Cruz JS, Lemos VS (2014) Thiamine deficiency leads to reduced nitric oxide production and vascular dysfunction in rats. Nutr Metab Cardiovasc Dis 24: 183-188. [Ref.]
- Sweet RL, Zastre JA (2013) HIF1-alpha-mediated gene expression induced by vitamin B1 deficiency. International J Vitam Nutr Res 83: 188-197. [Ref.]
- Kanngiesser M, Mair N, Lim HY, Zschiebsch K, Blees J, et al. (2014) Hypoxia-inducible factor 1 regulates heat and cold pain sensitivity and persistence. Antioxid Redox Signal 20: 2555-2571. [Ref.]
- de Andrade JA, Gayer CR, Nogueira NP, Paes MC, Bastos VL, et al. (2014) The effect of thiamine deficiency on inflammation, oxidative stress and cellular migration in an experimental model of sepsis. J Inflamm (Lond) 11:11. [Ref.]
- Gangolf M, Czerniecki J, Radermecker M, Detry O, Nisolle M, et al. (2010) Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells. PLoS One 5: e13616. [Ref.]
- Lonsdale D (2007) Three case reports to illustrate clinical applications in the use of erythrocyte transketolase. Evid Based Complement Alternat Med 4: 247-250. [Ref.]
- Peters R A (1938) The catatorulin test for vitamin B1. Biochem J 32: 2031-2036. [Ref.]
- Lonsdale D (2006) A review of the biochemistry, metabolism and clinical benefits of thiamin(e) and its derivatives. Evid Based Complement Alternat Med 3: 49-59. [Ref.]
- Casteels M, Sniekers M, Fraccascia P, Mannaerts GP, Van Veldhoven PP (2007) The role of 2-hydroxyacyl-CoA lyase, a thiamine pyrophosphate-dependent enzyme, in the peroxisomal metabolism of 3-methyl-branched fatty acids and 2-hydroxy straight-chain fatty acids. Biochem Soc Trans 35: 876-880. [Ref.]
- Fraccascia P, Sniekers M, Casteels M, Van Veldhoven PP (2007) Presence of thiamine pyrophosphate in mammalian peroxisomes. BMC Biochem 8: 10. [Ref.]
- Fraccascia P, Casteels M, De Schryver E, Van Veldhoven PP (2011) Role of thiamine pyrophosphate in oligomerisation. Biochim Biophys Acta 1814: 1226-1233. [Ref.]
- Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, et al. (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334: 98-101. [Ref.]
- Szutowicz A, Bielarczyk H, Jankowska-Kulawy A, Pawelczyk T, Ronowska A (2013) Acetyl CoA the key factor for survival or death of cholinergic neurons in course of neurodegenerative diseases. Neurochem Res 38: 1523-1542. [Ref.]
- Riley CM, Day RL, Greeley DM, et al. (1949) Central autonomic dysfunction with defective lacrimation. Report of five cases. Pediat 3: 468-478. [Ref.]
- Riley CM, Moore RH (1966) Familial dysautonomia differentiated from related disorders. Pediat 37: 435-446. [Ref.]
- Bisschop PH, Fliers E, Kalsbeek A (2015) Autonomic regulation of hepatic glucose production. Compr Physiol 5: 147-165. [Ref.]
- Coghlan HC, Phares P, Cowley M, Copley D, James TN (1979) Dysautonomia in mitral valve prolapse. Am J Med 67: 236-244. [Ref.]
- Coghlan HC, Natello G (1991-1992) Erythrocyte magnesium in symptomatic patients with primary mitral valve prolapse: relationship to symptoms, mitral leaflet sickness, joint hypermobility and autonomic regulation. Magnes Trace Elem 10: 205-214. [Ref.]
- Colasanti A, Esquivel G, Schruers KJ, Griez EJ (2012) On the psychotropic effects of carbon dioxide. Curr Pharm Des 18: 5627- 5637. [Ref.]
- Johnson TS, Young JB, Landsberg L (1983) Sympathoadrenal responses to acute and chronic hypoxia in the rat. J Clin Invest 71: 1263-1272. [Ref.]
- Ceylan M, Sener S, Bayraktar C Kavutcu M (2010) Oxidative imbalance in child and adolescent patients with attention-deficit/ hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 54: 1491-1494. [Ref.]
- Cemek M, Dede S, Baviroglu F, Caksen H, Cemek F,Yuca K (2005) Oxidant and antioxidant levels in children with acute otitis media and tonsillitis: a comparative study. Int J Pediatr Otorhinolaryngol 69: 823- 827. [Ref.]
- Lonsdale D, Faulkner WR, Price JW, Smeby RR (1969) Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperalaninemia, and hyperalaninuria. Pediatrics 43: 1025-1034. [Ref.]
- Ram G, Lee J, Ott M, Brown-Whitehorn TF, Cianferoni A, et al. (2015) Seasonal exacerbation of esophageal eosinophilia in children with eosinophilic esophagitis and allergic rhinitis. Ann Allergy Asthma Immunol 115: 224-228. [Ref.]
- Bernstein JA, Singh U (2015) Neural Abnormalities in Nonallergic Rhinitis. Curr Allergy Asthma Rep 15: 18. [Ref.]
- Lonsdale D (2004) Thiamin tetrahydrofurfuryl disulfide: a little known therapeutic agent. Med Sci Monit 10: 199-203. [Ref.]
- Lonsdale D (2015) Thiamine and magnesium deficiencies: keys to disease. Med Hypotheses 84: 129-134. [Ref.]
- Fernhoff PM, Lubitz D, Danner DJ, Dembure PP, Schwartz HP, et al. (1985) Thiamine response in maple syrup urine disease. Pediatr Res 19: 1011-1016. [Ref.]
- Banka S, de Goede C, Yue WW, Morris AA, von Bremen B, et al. (2014) Expanding the clinical and molecular spectrum of thiamine pyrophosphate kinase deficiency: a treatable neurological disorder caused by TPK1 mutations. Mol Genet Metab 113: 301-306. [Ref.]
- Hills JI, Golub MS, B ettendorff L, Keen CL (2012) The effect of thiamine tetrahydrofurfuryl disulfide on behavior of juvenile DBA/2J mice. Neurotoxicol Teratol 34: 242-252. [Ref.]
- Nozaki S, Mizuma H, Tanaka M, Jin G, Tahara T, et al. (2009) Thiamine tetrahydrofurfuryl disulfide improves energy metabolism and physical performance during physical-fatigue loading in rats. Nutr Res 29: 867- 872. [Ref.]
- Lonsdale D (1982) Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/2J mice. Dev Pharmacol Ther 4: 28-36. [Ref.]
- Fraser DA, Diep LM, Hovden IA, Nilsen KB, Sveen KA, et al. (2012) The effects of long-term oral benfotiamine supplementation on peripheral nerve function and inflammatory markers in patients with type I diabetes: a 24-month, double-blind, randomized, placebocontrolled trial. Diabetes Care 35: 1095-1097. [Ref.]
- Bozic I, Savic D, Laketa D, Bjelobaba I, Milenkovic I, et al. (2015) Benfotiamine attenuates inflammatory response in LPS stimulated BV-2 microglia. PLoS One 10: e0118372. [Ref.]
- Volvert ML, Seyen S, Piette M, Evrard B, Gangolf M, et al. (2008) Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives. BMC Pharmacol 8: 10. [Ref.]
- Matsui K, Nakahara H, Watanabe H, Tamatsu H, Nakazawa M, et al. (1985) Inhibition by thiamine tetrahydrofurfuryl disulfide (TTFD) of the arachidonic acid cascade-line activation as evidenced in the heartlung preparation of the dog. J Pharmacol 39: 375-379. [Ref.]
- Coskun R, Turan MI, Turan IS, Gulapoglu M (2014) The protective effect of thiamine pyrophosphate, but not thiamine, against cardio toxicity induced with cisplatin in rats. Drug Chem Toxicol 37: 290-294. [Ref.]
- Baker H, Frank O (1976) Absorption, utilization and clinical effectiveness of allithiamines compared to water-soluble thiamines. J Nutr Sci Vitaminol (Tokyo) SUPPL: 63-68. [Ref.]
- Slack MA, Ogbogu PU, Phillips G, Platts-Mills TA, Erwin EA (2015) Serum vitamin D levels in a cohort of adult and pediatric patients with eosinophilic esophagitis. Ann Allergy Asthma Immunol 115: 45-50. [Ref.]
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Aritcle Type: Case Report
Citation: Lonsdale D (2016) Is Eosinophilic Esophagitis a Sugar Sensitive Disease?. J Gastric Disord Ther 2 (1): doi http://dx.doi.org/10.16966/2381-8689.114
Copyright: © 2016 Lonsdale D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.