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1. Ann Neurol. 2003 Jul;54(1):19-29.
Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy.
Koike H, Iijima M, Sugiura M, Mori K, Hattori N, Ito H, Hirayama M, Sobue G.
Department of Neurology, Nagoya University, Graduate School of Medicine, Nagoya, Japan.
Characteristics of alcoholic neuropathy have been obscured by difficulty in isolating them from features of thiamine-deficiency neuropathy. We assessed 64 patients with alcoholic neuropathy including subgroups without (ALN) and with (ALN-TD) coexisting thiamine deficiency. Thirty-two patients with nonalcoholic thiamine-deficiency neuropathy (TDN) also were investigated for comparison. In ALN, clinical symptoms were sensory-dominant and slowly progressive, predominantly impairing superficial sensation (especially nociception) with pain or painful burning sensation. In TDN, most cases manifested a motor-dominant and acutely progressive pattern, with impairment of both superficial and deep sensation. Small-fiber-predominant axonal loss in sural nerve specimens was characteristic of ALN, especially with a short history of neuropathy; long history was associated with regenerating small fibers. Large-fiber-predominant axonal loss predominated in TDN. Subperineurial edema was more prominent in TDN, whereas segmental de/remyelination resulting from widening of consecutive nodes of Ranvier was more frequent in ALN. Myelin irregularity was greater in ALN. ALN-TD showed a variable mixture of these features in ALN and TDN. We concluded that pure-form of alcoholic neuropathy (ALN) was distinct from pure-form of thiamine-deficiency neuropathy (TDN), supporting the view that alcoholic neuropathy can be caused by direct toxic effect of ethanol or its metabolites. However, features of alcoholic neuropathy is influenced by concomitant thiamine-deficiency state, having so far caused the obscure clinicopathological entity of alcoholic neuropathy.
2. Nippon Jinzo Gakkai Shi. 2003;45(4):393-7.
[Acute encephalopathy due to thiamine deficiency with hyperammonemia in a chronic hemodialysis patient: a case report]
[Article in Japanese]
Ookawara S, Suzuki M, Saitou M.
Department of Internal Medicine, Nishikawa Town Hospital, Japan.
Hemodialysis(HD) patients are at risk for thiamine deficiency because of low intake and accelerated loss of thiamine during HD. We report here an HD patient, an 82-year-old woman, who developed acute encephalopathy due to thiamine deficiency with hyperammonemia. She was admitted to Nishikawa Town Hospital due to pneumonia and was treated with ABPC/SBT for one week. While she was cured of pneumonia, she had a persistently poor appetite. On the twenty-fourth day after admission, HD with intradialytic parenteral nutrition(IDPN), which consisted of 10% glucose 500 ml, in order to correct her malnutrition, was started. She suddenly presented confusion, speech disturbance and ophthalmoplegia. HD with IDPN was stopped after two hours because of her symptoms. Laboratory studies disclosed plasma glucose of 186 mg/dl and serum ammonium of 155 micrograms/dl. Arterial blood gas analysis(inhaling 3 l/min O2) showed severe metabolic acidosis and respiratory acidosis (pH 7.138, pCO2 44.8 mmHg, pO2 108.9 mmHg, HCO3- 15.1 mmol/l). Her malnutrition, unexplained metabolic acidosis and neurological presentation raised the suspicion of acute encephalopathy due to thiamine deficiency. Fursultiamine 100 mg was administered intravenously. After two hours, metabolic acidosis disappeared (pH 7.437, pCO2 33.9 mmHg, pO2 161.0 mmHg, HCO3- 22.9 mmol/l), and she regained her clear consciousness and serum ammonium decreased at 16 micrograms/dl on the next morning. Serum lactate and thiamine level were shown later to be 57.5 mg/dl and 27 nmol/l, respectively. Her clinical course suggests that the glucose load including IDPN may have caused deterioration of the neurological disorder under the condition of thiamine deficiency. Furthermore, it is possible that a relationship exists between thiamine deficiency and hyperammonemia.
3. Harefuah. 2003 May;142(5):329-31, 400, 399.
[Thiamine deficiency among Chinese workers in Israel]
[Article in Hebrew]
Kleiner-Baumgarten A, Sidi A, Abu-Shakra M, Klain M, Bilenko N, Sela BA.
Internal Medicine Day-Hospital Unit, Soroka University Medical Center, Faculty of Health Sciences, Ben Gurion University, Beer Sheva.
The death of a 23-year-old Chinese construction worker in southern Israel from refractory metabolic acidosis after presenting symptoms of edema and loss of sensation in his legs raised the suspicion of Beriberi disease. As thiamine deficiency was suspected, two other Chinese workers from the same construction site, who also complained of pain and swelling in their legs were tested and found to have a significant deficiency. In addition 56.5% of 46 Chinese workers at the site were found to have a thiamine deficiency without any significant clinical symptoms. A nutritional evaluation demonstrated a lack of thiamine in the workers diet due to a limited variety of food, their dietary preferences, and cooking style. There was also a lack of attention given to providing essential nutrients including thiamine by their employees. Clinicians must be aware that thiamine deficiency and beriberi disease may be common in this apparently healthy population.
4. J Neurol Neurosurg Psychiatry. 2003 May;74(5):674-6.
Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?
Ishibashi S, Yokota T, Shiojiri T, Matunaga T, Tanaka H, Nishina K, Hirota H, Inaba A, Yamada M, Kanda T, Mizusawa H.
Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.
5. J Clin Pharm Ther. 2003 Feb;28(1):47-51.
Effect of intravenous infusions of thiamine on the disposition kinetics of thiamine and its pyrophosphate.
Drewe J, Delco F, Kissel T, Beglinger C.
Division of Clinical Pharmacology and Toxicology, University Clinic, Kantonsspital Basel and Institute for Clinical Pharmacy, University of Basel, Basel, Switzerland. juergen.drewe@unibas.ch
BACKGROUND: Thiamine supplementation is necessary in patients with thiamine deficiency syndromes. Experimental evidence suggests that tissue uptake and the elimination of thiamine are dose-dependent. AIM: The aim of the present study was to investigate the effect of different i.v. infusion rates of thiamine on blood concentrations of thiamine and its active metabolite thiamine pyrophosphate (TPP) and on renal excretion of thiamine. METHODS: Twelve healthy subjects received in a two-period block randomized study 150 mg thiamine intravenously over either 1 or 24 h. RESULTS: The maximum blood concentrations (Cmax) of thiamine were significantly higher after the more rapid infusion (RI; 2300 ng/mL) than after the slower infusion (SI; 177 ng/mL). The AUC of thiamine was identical after both infusion protocols. There was a slightly (10%) increased AUC of TPP (P < 0.08) after SI, whereas C(max) values were comparable. Urinary excretion of thiamine was significantly decreased from 83.6% of the applied dose after RI to 57.6% after the SI. CONCLUSIONS: Our data suggest an increased tissue uptake of thiamine when it is given as an SI compared with a RI of the same dose. It is concluded, therefore, that an SI of thiamine may be superior to RI or bolus injections to treat severe deficiency syndromes.
6. Ann Cardiol Angeiol (Paris). 2001 Apr;50(3):160-8.
[Is thiamine supplementation necessary in patient with cardiac insufficiency?]
[Article in French]
Blanc P, Boussuges A.
Service de reanimation polyvalente, service de cardiologie, CHD Felix Guyon, 97405 Saint-Denis, La Reunion, France. ph-blanc@chd-fguyon.fr
Interest has recently risen regarding thiamine deficiency in patients with cardiac deficiency who are receiving long-term diuretic therapy. Thiamine deficiency can lead biventricular myocardial failure (cardiac beriberi), and treatment consists of thiamine administration. Studies have shown that long-term furosemide use may be associated with thiamine deficiency through urinary loss, contributing to cardiac insufficiency in patients with congestive heart failure. Thiamine supplementation could improved left ventricular function. However, the results of those studies are controversial, and none study have till proved the clinical impact of a systematic administration of thiamine in a cohort of patients with cardiac insufficiency. To date, and waiting for available literature, thiamine administration should be consider in patients at risk for thiamine deficiency (elderly, malnourished, alcoholic), and in patients receiving very large doses of diuretics.
7. Psychiatr Genet. 2002 Dec;12(4):217-24.
Individual susceptibility to Wernicke-Korsakoff syndrome and alcoholism-induced cognitive deficit: impaired thiamine utilization found in alcoholics and alcohol abusers.
Heap LC, Pratt OE, Ward RJ, Waller S, Thomson AD, Shaw GK, Peters TJ.
Department of Clinical Biochemistry, Kings College School of Medicine and Dentistry, London, UK.
To investigate mechanisms predisposing to alcoholic brain damage, thiamine (vitamin B1 ), riboflavin (vitamin B2 ) and pyridoxine (vitamin B6 ) status was compared in persistent alcohol misusers (PAM) admitted for detoxification without evidence of significant brain damage, in alcoholics known to have severe chronic brain damage (BDAM), and in age, gender and ethnicity matched controls. Thus, activities of thiamine-dependent transketolase (ETK), riboflavin-dependent glutathione reductase, and pyridoxine-dependent aspartate amino transferase were assayed, together with the enzyme activities following addition of the appropriate co-factor. Twenty per cent of the PAM group had an abnormally low ETK activity and an abnormally high activation ratio, while 45% were abnormal in either one or both parameters. An additional 10% of the PAM group had an abnormally high activation ratio but normal ETK activity, as did 30% of the BDAM group. These subgroups of alcohol misusers may have increased requirements for thiamine secondary to an abnormality of the transketolase protein that may predispose such patients to alcoholic brain damage. There was no evidence of riboflavin or pyridoxine deficiency in either of the patient groups. We conclude that thiamine deficiency was commonly present in the alcoholic patients, and that a subgroup of patients may be predisposed to more severe brain damage as a consequence of abnormalities in the transketolase protein.
8. Panminerva Med. 2002 Dec;44(4):295-300.
Mitochondrial diabetes, diabetes and the thiamine-responsive megaloblastic anaemia syndrome and MODY-2. Diseases with common pathophysiology?
Maassen JA.
Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden and EVM Institute, Medisch Centrum, Vrije Universiteit, Amsterdam, the Netherlands. J.A.Maassen@lumc.nl
Diabetes represents a conglomerate of diseases with chronic hyperglycaemia as hallmark. The present review discusses those diabetic cases that associate with variants in genes that affect the magnitude of the glycolytic flux and oxidative disposal of glucose by mitochondria in pancreatic beta-cells. These genetic variants result in an attenuated secretion of insulin in response to glucose stimulation. The diabetic states that associate with these genetic variants are MODY 2, thiamine responsive anaemia syndrome (TRAS) and mitochondrial diabetes. These disease states highlight the critical contribution of the carbohydrate flux through glycolysis and mitochondria and its coupling to ATP production in determining insulin secretion.
9. Biochim Biophys Acta. 2002 Oct 9;1588(1):79-84.
Thiamine-responsive pyruvate dehydrogenase deficiency in two patients caused by a point mutation (F205L and L216F) within the thiamine pyrophosphate binding region.
Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Ogawa Y, Kitamura S, Takada E, Horii Y, Kuroda Y.
Department of Pediatrics, School of Medicine, University of Tokushima, Kuramoto Cho 3, Tokushima, Japan. enaito@clin.med.tokushima-u.ac.jp
The human pyruvate dehydrogenase complex (PDHC) catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment is very effective for some patients with PDHC deficiency. Among these patients, five mutations of the pyruvate dehydrogenase (E1)alpha subunit have been reported previously: H44R, R88S, G89S, R263G, and V389fs. All five mutations are in a region outside the thiamine pyrophosphate (TPP)-binding region of the E1alpha subunit.We report the biochemical and molecular analysis of two patients with clinically thiamine-responsive lactic acidemia. The PDHC activity was assayed using two different concentrations of TPP. These two patients displayed very low PDHC activity in the presence of a low (1 x 10(-4) mM) TPP concentration, but their PDHC activity significantly increased at a high (0.4 mM) TPP concentration. Therefore, the PDHC deficiency in these two patients was due to a decreased affinity of PDHC for TPP. Treatment of both patients with thiamine resulted in a reduction in the serum lactate concentration and clinical improvement, suggesting that these two patients have a thiamine-responsive PDHC deficiency. The DNA sequence of these two male patients' X-linked E1alpha subunit revealed a point mutation (F205L and L216F) within the TPP-binding region in exon 7.
10. Neuroendocrinol Lett. 2002 Aug;23(4):303-8.
Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study.
Lonsdale D, Shamberger RJ, Audhya T.
Preventive Medicine Group, 24700 Center Ridge Road, Westlake, OH 44145, USA. dlonsdale@pol.net
OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined. RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.
11. Klin Med (Mosk). 2002;80(7):39-42.
[Urine levels of thiamine and riboflavine in diuretic therapy of patients with cardiovascular diseases]
[Article in Russian]
Shikh EV.
Diuretic therapy entails decreased plasma concentrations of thiamine and riboflavine. Vitamins eliminated with urine more rapidly when diuresis accelerates. This process is not related to diuresis cause. A linear relationship exists between diuresis intensity and amount of eliminated thiamine and riboflavine. Thus it is shown that diuretic therapy provokes thiamine and riboflavine elimination from the body.
12. J Neurol Sci. 2002 Sep 15;201(1-2):33-7.
Diagnosis and molecular analysis of three male patients with thiamine-responsive pyruvate dehydrogenase complex deficiency.
Naito E, Ito M, Yokota I, Saijo T, Ogawa Y, Kuroda Y.
Department of Pediatrics, School of Medicine, University of Tokushima, Kuramoto Cho 3, 770-8503, Tokushima, Japan. enaito@clin.med.tokushima-u.ac.jp
Pyruvate dehydrogenase complex (PDHC) deficiency is a major cause of congenital lactic acidemia in children. PDHC catalyzes the thiamine-dependent decarboxylation of pyruvate. Thiamine treatment was effective for some patients with PDHC deficiency. We reexamined 30 patients with congenital lactic acidemia of unknown origin who had normal PDHC activity in their cultured fibroblasts using a routine assay with a high (0.4 mM) thiamine pyrophosphate (TPP) concentration. We measured the activity of PDHC in the presence of a low (1x10(-4) mM) TPP concentration, and analyzed for mutations in the E1alpha subunit gene. Three males had low PDHC activity in the presence of 1x10(-4) mM TPP. The DNA sequence of these three patients' X-linked E1alpha subunit revealed a substitution of alanine for valine at position 71 (V71A) in exon 3, phenylalanine for cysteine at position 101 (C101F) in exon 4, and glycine for arginine at position 263 (R263G) in exon 8, respectively. Thiamine treatment was effective in these three patients. Therefore, they had a thiamine-responsive PDHC deficiency due to a point mutation in the E1alpha subunit gene. PDHC activity should be measured at a low TPP concentration to detect thiamine-responsive PDHC deficiency so that thiamine treatment can be initiated as soon as possible.
13. Gastric Cancer. 2002;5(2):77-82.
Reduced thiamine (vitamin B1) levels following gastrectomy for gastric cancer.
Iwase K, Higaki J, Yoon HE, Mikata S, Miyazaki M, Kamiike W.
Department of Surgery, Rinku General Medical Center, Izumisano Municipal Hospital, 2-23 Rinku-Orai-Kita, Izumisano, Osaka 598-8577, Japan.
BACKGROUND: Vitamin B1 deficiency is well known as a possible complication following gastric restrictive surgery for morbid obesity; however, reduced vitamin B1 levels in patients who have undergone gastrectomy for gastric cancer have not been discussed previously.METHODS: Serum vitamin B1 levels were determined after the return to normal daily activity in 54 patients with distal gastrectomy for gastric cancer, 32 patients with total gastrectomy for gastric cancer, and 30 patients with radical surgery for colorectal cancer. Changes from serum vitamin B1 levels before operation to those after return to normal daily activity, without nutritional support, were investigated in 25 patients with gastrectomy for gastric cancer and 26 patients with radical surgery for colorectal cancer.RESULTS: Decreased serum vitamin B1 levels, below the normal range, were recognized in 7 of the 54 distally gastrectomized patients and in 5 of the 32 totally gastrectomized patients, whereas no such decrease was recognized in any patient after colorectal surgery. Decreased serum vitamin B1 level was recognized within 6 months after the operation in 6 of the 7 distally gastrectomized patients showing a decreased vitamin B1 level and in 3 of the 5 totally gastrectomized patients showing a decreased vitamin B1 level. Postoperative serum vitamin B1 levels were significantly lower than those before operation in patients with gastrectomies, whereas there was no significant difference in serum vitamin B1 levels before and after the surgeries in patients with surgery for colorectal cancer.CONCLUSION: Vitamin B1 levels may be reduced in gastrectomized patients, especially within 6 months after operation, even after their return to normal daily activity without nutritional support.
14. J Neural Transm. 2002 Jul;109(7-8):1035-44.
Cerebrospinal fluid levels of thiamine in patients with Alzheimer's disease.
Molina JA, Jimenez-Jimenez FJ, Hernanz A, Fernandez-Vivancos E, Medina S, de Bustos F, Gomez-Escalonilla C, Sayed Y.
Department of Neurology, Hospital Universitario Doce de Octubre, E-28030 Madrid, Spain.
Thiamine is an essential cofactor for several important enzymes involved in brain oxidative metabolism, such as the alpha-ketoglutarate dehydrogenase complex (KGDHC), pyruvate-dehydrogenase complex (PDHC), and transketolase. Some investigators reported decreased thiamine-diphosphate levels and decreased activities of KGDHC, pyruvate-dehydrogenase complex and transketolase in the brain tissue of Alzheimer's disease (AD) patients. We measured cerebrospinal (CSF) levels of thiamine-diphosphate, thiamine-monophosphate, free thiamine, and total thiamine, using ion-pair reversed phase high performance liquid chromatography, in 33 patients with sporadic AD and 32 matched controls.The mean CSF levels of thiamine-derivatives did not differ significantly from those of controls, while the mean plasma levels of thiamine-diphosphate, free and total thiamine were significantly lower in the AD-patient group. CSF and plasma thiamine levels were not correlated with age, age at onset, duration of the disease, and scores of the MiniMental State Examination, with the exception of plasma thiamine-diphosphate with MiniMental State Examination (r = 0.41, p < 0.05) in the AD-patients group. CSF and plasma values did not predict dementia progression, assessed with the MiniMental State Examination scores. These results suggest that CSF thiamine levels are not related with the risk for and the progression of AD.
15. AIDS Read. 2002 May;12(5):222-4.
High doses of riboflavin and thiamine may help in secondary prevention of hyperlactatemia.
McComsey GA, Lederman MM.
Pediatric Infectious Diseases Division, Rainbow Babies and Children's Hospital, Western Reserve University, Cleveland, USA.
Lactic acidosis is the most dramatic manifestation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction. The optimal management of subjects who recover from an episode of lactic acidosis--or its milder form, symptomatic hyperlactatemia--remains unclear. Most physicians opt to restart NRTI-sparing regimens, but such an option may not be available for heavily antiretroviral-experienced patients. Therefore, there is a need to investigate ways to prevent the recurrence of hyperlactatemia in patients who require NRTI-based therapy.
16. BMC Biochem. 2002 Apr 25;3(1):8.
Mitochondria from cultured cells derived from normal and thiamine-responsive megaloblastic anemia individuals efficiently import thiamine diphosphate.
Song Q, Singleton CK.
Department of Biological Sciences, Vanderbilt University, VU Station B 351634, Nashville TN 37235-1634, USA. tony.song@vanderbilt.edu
BACKGROUND: Thiamine diphosphate (ThDP) is the active form of thiamine, and it serves as a cofactor for several enzymes, both cytosolic and mitochondrial. Isolated mitochondria have been shown to take up thiamine yet thiamine diphosphokinase is cytosolic and not present in mitochondria. Previous reports indicate that ThDP can also be taken up by rat mitochondria, but the kinetic constants associated with such uptake seemed not to be physiologically relevant. RESULTS: Here we examine ThDP uptake by mitochondria from several human cell types, including cells from patients with thiamine-responsive megaloblastic anemia (TRMA) that lack a functional thiamine transporter of the plasma membrane. Although mitochondria from normal lymphoblasts took up thiamine in the low micromolar range, surprisingly mitochondria from TRMA lymphoblasts lacked this uptake component. ThDP was taken up efficiently by mitochondria isolated from either normal or TRMA lymphoblasts. Uptake was saturable and biphasic with a high affinity component characterized by a Km of 0.4 to 0.6 microM. Mitochondria from other cell types possessed a similar high affinity uptake component with variation seen in uptake capacity as revealed by differences in Vmax values. CONCLUSIONS: The results suggest a shared thiamine transporter for mitochondria and the plasma membrane. Additionally, a high affinity component of ThDP uptake by mitochondria was identified with the apparent affinity constant less than the estimates of the cytosolic concentration of free ThDP. This finding indicates that the high affinity uptake is physiologically significant and may represent the main mechanism for supplying phosphorylated thiamine for mitochondrial enzymes.
17. Dig Dis Sci. 2002 Mar;47(3):543-8.
Thiamine deficiency in hepatitis C virus and alcohol-related liver diseases.
Levy S, Herve C, Delacoux E, Erlinger S.
Department of Hepatology and INSERM U-481 and Hopital Beaujon, Clichy, France.
Thiamine deficiency is a common feature in chronic alcoholic patients, and its pathophysiology remains poorly understood. Until now, thiamine deficiency has been considered to be mainly the result of alcoholism irrespective of the underlying liver disease. The aims of the study were to compare the prevalence of thiamine deficiency in alcohol- and hepatitis C virus-(HCV-) related cirrhosis and in patients with chronic hepatitis C without cirrhosis. Forty patients with alcoholic cirrhosis (group A), 48 patients with HCV-related cirrhosis (group B), and 59 patients with chronic hepatitis C without cirrhosis (group C) were included prospectively. Thiamine status was evaluated by concomitant determination of erythrocyte transketolase activity, thiamine diphosphate (TDP) effect, and direct measurement of erythrocyte thiamine and its phosphate esters by HPLC. Thiamine was mainly present in erythrocytes in its diphosphorylated form. Prevalence of thiamine deficiency and levels of TDP in thiamine-deficient patients were similar in patients of group A (alcoholic cirrhosis) and of group B (viral C cirrhosis). None of the patients with chronic hepatitis (group C) was deficient. Thiamine deficiency was not correlated with the severity of the liver disease or disease activity. No impairment of thiamine phosphorylation was found in the three groups. conclusion, alcoholic or HCV-related cirrhotics have the same range of thiamine deficiency, while no patient without cirrhosis has thiamine deficiency, and impaired phosphorylation does not account for the deficiency observed in cirrhotics. We suggest that thiamine should be given to patients with cirrhosis irrespective of its cause.
18. Curr Mol Med. 2001 May;1(2):197-207.
Molecular mechanisms of thiamine utilization.
Singleton CK, Martin PR.
Department of Biological Science, Vanderbilt University, Nashville, TN 37235, USA. Charles.K.Singleton@Vanderbilt.edu
Thiamine is required for all tissues and is found in high concentrations in skeletal muscle, heart, liver, kidneys and brain. A state of severe depletion is seen in patients on a strict thiamine-deficient diet in 18 days, but the most common cause of thiamine deficiency in affluent countries is alcoholism. Thiamine diphosphate is the active form of thiamine, and it serves as a cofactor for several enzymes involved primarily in carbohydrate catabolism. The enzymes are important in the biosynthesis of a number of cell constituents, including neurotransmitters, and for the production of reducing equivalents used in oxidant stress defenses and in biosyntheses and for synthesis of pentoses used as nucleic acid precursors. Because of the latter fact, thiamine utilization is increased in tumor cells. Thiamine uptake by the small intestines and by cells within various organs is mediated by a saturable, high affinity transport system. Alcohol affects thiamine uptake and other aspects of thiamine utilization, and these effects may contribute to the prevalence of thiamine deficiency in alcoholics. The major manifestations of thiamine deficiency in humans involve the cardiovascular (wet beriberi) and nervous (dry beriberi, or neuropathy and/or Wernicke-Korsakoff syndrome) systems. A number of inborn errors of metabolism have been described in which clinical improvements can be documented following administration of pharmacological doses of thiamine, such as thiamine-responsive megaloblastic anemia. Substantial efforts are being made to understand the genetic and biochemical determinants of inter-individual differences in susceptibility to development of thiamine deficiency-related disorders and of the differential vulnerabilities of tissues and cell types to thiamine deficiency.
19. Neurochem Int. 2002 May;40(6):493-504.
Interactions of oxidative stress with thiamine homeostasis promote neurodegeneration.
Gibson GE, Zhang H.
Burke Medical Research Institute, Weil Medical College, Cornell University, 785 Mamaroneck Avenue, White Plains, NY 10605, USA. ggibson@med.cornell.edu
Thiamine-dependent processes are diminished in brains of patients with several neurodegenerative diseases. The decline in thiamine-dependent enzymes can be readily linked to the symptoms and pathology of the disorders. Why the reductions in thiamine linked processes occur is an important experimental and clinical question. Oxidative stress (i.e. abnormal metabolism of free radicals) accompanies neurodegeneration and causes abnormalities in thiamine-dependent processes. The vulnerability of thiamine homeostasis to oxidative stress may explain deficits in thiamine homeostasis in numerous neurological disorders. The interactions of thiamine with oxidative processes may be part of a spiral of events that lead to neurodegeneration, because reductions in thiamine and thiamine-dependent processes promote neurodegeneration and cause oxidative stress. The reversal of the effects of thiamine deficiency by antioxidants, and amelioration of other forms of oxidative stress by thiamine, suggest that thiamine may act as a site-directed antioxidant. The data indicate that the interactions of thiamine-dependent processes with oxidative stress are critical in neurodegenerative processes.
20. Acta Diabetol. 2001;38(3):135-8.
Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.
Pomero F, Molinar Min A, La Selva M, Allione A, Molinatti GM, Porta M.
WHO Collaborating Centre for Diabetes-Related Blindness, Department of Internal Medicine, University of Turin, Italy.
We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.
21. Int J Geriatr Psychiatry. 2002 Feb;17(2):189-92.
Using thiamine to reduce post-ECT confusion.
Linton CR, Reynolds MT, Warner NJ.
Cognitive side-effects are commonly seen following electroconvulsive therapy which convey no therapeutic benefit but are troublesome to both patient and clinician. Various efforts have been made in the past to minimize these symptoms. Although modification of technical parameters related to ECT administration has led to some limited improvement in this regard, attention is now being increasingly focussed on pharmacological approaches. A number of agents have been explored in this context, however, as far as we are aware, the use of thiamine has not yet been investigated. We present three cases of elderly patients undergoing ECT for major depression in whom thiamine administration was associated with beneficial effects on post-ECT confusion. We review the evidence suggesting that thiamine deficiency may be implicated in the confusional state following ECT and recommend that consideration be given to its use in preventing and treating this problematic side-effect, especially in elderly patients. Copyright 2002 John Wiley & Sons, Ltd.
22. J Nutr Health Aging. 2002;6(1):75-7.
Reduced serum concentrations of riboflavine and ascorbic acid, and blood thiamine pyrophosphate and pyridoxal-5-phosphate in geriatric patients with and without pressure sores.
Selvaag E, Bohmer T, Benkestock K.
Department of medicine, Aker University Hospital, Oslo, Norway.
BACKGROUND: Patients with pressure sores have as part of their treatment been reefed with energy and proteins with varying result. It has been uncertain, however, to what an extent these patients also were depleted of micronutrients which might be critical for ulcer healing. OBJECTIVE: To study the nutritional intake and nutritional status of a number of micronutrients in geriatric pressure sore patients and in matched controls. DESIGN: The nutritional intake and nutritional status as anthropometric measures, serum conc. of albumin, zinc, and of vitamins (ascorbic acid, riboflavin, calcidiol), were measured. Thiamin pyrophosphate and pyridoxal-5-phosphate were determined in whole blood from 11 geriatric in-patients with pressure sores and 11 matched controls. RESULTS: The serum conc. of ascorbic acid was significantly (p< 0.05) more reduced in pressure sore patients (mean+/-S.D.) 4.2+/-3.4 (ug/ml) than in control patients 7.4+/-5.4 (ug/ml) which still was lower than in a reference group (10.9+/-1.9) (ug/ml). In all the geriatric patients compared to the reference group, the conc. of serum-riboflavin was reduced to about 15 %, thiamine-pyrophosphate and pyridoxine-5-phosphate in whole blood and serum calcidiol to about 50 %, without any differences between the pressure sore patients and the matched controls. CONCLUSION: Refeeding of pressure sore patients who often are catabolic and have increased needs for protein and energy, should include micronutrients not only to cover recommended dietary allowances, but sufficient to reach normal nutritional status for the individual micronutrient.
23. Am J Kidney Dis. 2001 Nov;38(5):941-7.
Thiamine deficiency and unexplained encephalopathy in hemodialysis and peritoneal dialysis patients.
Hung SC, Hung SH, Tarng DC, Yang WC, Chen TW, Huang TP.
Department of Medicine, Division of Nephrology, TaipeiVeterans General Hospital, Taiwan.
Patients with end-stage renal disease undergoing regular dialysis are prone to encephalopathy, but the cause is often unclear. Dialysis patients are at risk for thiamine deficiency, which may mimic many uremic complications, including encephalopathy. To determine whether unexplained encephalopathy in regular dialysis patients is associated with thiamine deficiency, we conducted a prospective study that enrolled 30 consecutive dialysis patients with altered mental status admitted to a referred hospital during a 1-year period. A complete history, physical and neurological examinations, laboratory investigations, and computed tomographic scans or magnetic resonance imaging of the brain were obtained for each subject. In 10 of the 30 patients, diagnoses remained obscure after the initial workup. Manifestations included confusion, chorea, acute visual loss, rapidly progressive dementia, myoclonus, convulsions, and coma. Intravenous thiamine was administered to these 10 patients. All 10 patients had thiamine deficiency confirmed by a marked response to thiamine supplementation and/or a low serum thiamine concentration (35.3 +/- 6.0 nmol/L; normal, >50 nmol/L). Nine patients recovered, but one patient failed to respond because of delayed treatment. We conclude that in regular dialysis patients, unexplained encephalopathy can be mainly attributed to thiamine deficiency. This condition is fatal if unrecognized and can be successfully treated with prompt thiamine replacement.
24. Int J Vitam Nutr Res. 2001 Jul;71(4):217-21.
The thiamine status of adult humans depends on carbohydrate intake.
Elmadfa I, Majchrzak D, Rust P, Genser D.
Institute of Nutritional Sciences, University of Vienna.
Thiamine requirements for humans are generally expressed as absolute values per day (mg/d) or in relation to total caloric intake. Limited data are available on the relation between thiamine requirements and the intake of carbohydrates. This study was performed to investigate the influence of stepwise increases of carbohydrate intake on the status of thiamine in healthy volunteers under isocaloric conditions. During an adaptation phase of four days, the carbohydrate intake of twelve healthy volunteers (6 male, 6 female) was 55% of total energy intake. During the subsequent intervention periods, carbohydrate intake was increased to 65% of total energy for four days and to 75% for another four days. Thiamine intake, total energy intake, and physical activity were kept constant throughout the study. HPLC analysis was used to measure thiamine in plasma, urine and feces. Erythrocyte transketolase activity (ETK) was determined enzymatically. During the intervention periods thiamine decreased significantly (p < 0.05) in plasma (from 19.3 +/- 3.3 to 16.4 +/- 4.0 nmol/l) as well as in urine (from 72 +/- 56 to 58 +/- 21 mumol/mol creatinine). ETK and feces content of thiamine remained unchanged. An increase of dietary carbohydrate intake from 55% to 65% and 75%, respectively, of total caloric intake for four days per period at isocaloric conditions causes a decrease of plasma and urine levels of thiamine without affecting enzyme activities.
25. Postgrad Med J. 2001 Sep;77(911):582-5.
Thiamine deficiency in patients with B-chronic lymphocytic leukaemia: a pilot study.
Seligmann H, Levi R, Konijn AM, Prokocimer M.
Clinical Pharmacology Unit, Bnai Zion Medical Center, Technion Faculty of Medicine, Haifa, Israel. konijn@md2.huji.ac.il
Malignancy associated primary thiamine deficiency has been documented in several experimental tumours, sporadic clinical case reports, and in a number of patients with fast growing haematological malignancies. Thiamine status was assessed prospectively in 14 untreated B-chronic lymphocytic leukaemia (CLL) patients, and in 14 age matched control patients with non-malignant disease. Patients with any known cause of absolute, relative, or functional thiamine deficiency were excluded. High (>15%) thiamine pyrophosphate effect (TPPE), indicating thiamine deficiency, was found in five out of 14 CLL patients (35.7%) and in none of the controls (p=0.057). Mean (SD) TPPE in the thiamine deficient patients group was 21.6 (3.4)%. In all the patients, thiamine deficiency was subclinical. No correlates for the thiamine deficiency have been found save for an increment of more than 20% in the total leucocyte count over the preceding three months, which was found in all five thiamine deficient patients compared with only one of the nine non-thiamine deficient CLL patients. Thus, CLL patients may be prone to develop primary thiamine deficiency possibly promoted by the increased leucocytes span, which may increase thiamine consumption. Since even subclinical thiamine deficiency may be detrimental to the patient's clinical course, and in view of the theoretical danger of thiamine promoted tumour cell proliferation, further large scale studies are warranted to confirm this observation, and to elucidate the issue of thiamine supplementation to CLL patients.
26. J Neurol Neurosurg Psychiatry. 2001 Sep;71(3):357-62.
Postgastrectomy polyneuropathy with thiamine deficiency.
Koike H, Misu K, Hattori N, Ito S, Ichimura M, Ito H, Hirayama M, Nagamatsu M, Sasaki I, Sobue G.
Department of Neurology, Nagoya University School of Medicine, Nagoya 466-8550, Japan.
OBJECTIVE: Polyneuropathy has been reported after gastrectomy performed to treat various lesions. Although thiamine deficiency is a possible cause of this neuropathy, the pathogenesis still remains to be clarified. Seventeen patients with peripheral neuropathy with thiamine deficiency after gastrectomy are described. METHODS: Seventeen patients with polyneuropathy after gastrectomy accompanied by thiamine deficiency were selected. Patients were restricted to those with total or subtotal gastric resection to treat ulcer or neoplasm. Patients who had undergone operations to treat morbid obesity were excluded. RESULTS: Intervals between the operation and onset of neuropathy varied from 2 months to 39 years. Most patients did not seem malnourished. Serum concentrations of B vitamins other than thiamine were nearly normal. Symmetric motor-sensory polyneuropathy, predominantly involving the lower limbs, had progressed over intervals varying from 3 days to 8 years. Relative degrees of motor and sensory impairment also varied extensively. Some cases that progressed rapidly mimicked Guillain-Barre syndrome. Electrophysiological and pathological findings were those of axonal neuropathy. Substantial functional recovery from polyneuropathy was seen in most patients by 3 to 6 months after initiating thiamine supplementation. Motor recovery was better than sensory recovery. CONCLUSIONS: Various symptoms were seen in patients with postgastrectomy neuropathy. Thiamine deficiency should be considered in the differential diagnosis of motor-sensory polyneuropathy after gastrectomy.
27. Am J Physiol Cell Physiol. 2001 Sep;281(3):C786-92.
Mechanism of thiamine uptake by human jejunal brush-border membrane vesicles.
Dudeja PK, Tyagi S, Kavilaveettil RJ, Gill R, Said HM.
Department of Medicine, West Side Veterans Affairs Medical Center and University of Illinois at Chicago, 60612, USA. pkdudeja@uic.edu
Thiamine, a water-soluble vitamin, is essential for normal cellular functions, growth and development. Thiamine deficiency leads to significant clinical problems and occurs under a variety of conditions. To date, however, little is known about the mechanism of thiamine absorption in the native human small intestine. The objective of this study was, therefore, to characterize the mechanism of thiamine transport across the brush-border membrane (BBM) of human small intestine. With the use of purified BBM vesicles (BBMV) isolated from the jejunum of organ donors, thiamine uptake was found to be 1) independent of Na(+) but markedly stimulated by an outwardly directed H(+) gradient (pH 5.5(in)/pH 7.5(out)); 2) competitively inhibited by the cation transport inhibitor amiloride (inhibitor constant of 0.12 mM); 3) sensitive to temperature and osmolarity of the incubation medium; 4) significantly inhibited by thiamine structural analogs (amprolium, oxythiamine, and pyrithiamine), but not by unrelated organic cations (tetraethylammonium, N-methylnicotinamide, or choline); 5) not affected by the addition of ATP to the inside and outside of the BBMV; 6) potential insensitive; and 7) saturable as a function of thiamine concentration with an apparent Michaelis-Menten constant of 0.61 +/- 0.08 microM and a maximal velocity of 1.00 +/- 0.47 pmol. mg protein(-1). 10 s(-1). Carrier-mediated thiamine uptake was also found in BBMV of human ileum. These data demonstrate the existence of a Na(+)-independent, pH-dependent, amiloride-sensitive, electroneutral carrier-mediated mechanism for thiamine absorption in native human small intestinal BBMV.
28. J Biol Chem. 2001 Oct 5;276(40):37186-93. Epub 2001 Jul 31.
Identification of a mouse thiamine transporter gene as a direct transcriptional target for p53.
Lo PK, Chen JY, Tang PP, Lin J, Lin CH, Su LT, Wu CH, Chen TL, Yang Y, Wang FF.
Institute of Biochemistry, National Yang Ming University, Shih-Pai, Taipei 112, Taiwan.
p53 tumor suppressor is a transcription factor that functions, in part, through many of its downstream target genes. We have identified a p53-inducible gene by performing mRNA differential display on IW32 murine erythroleukemia cells containing a temperature-sensitive p53 mutant allele, tsp53(Val-135). Sequence analysis of the full-length cDNA revealed its identity as the mouse homologue of the human thiamine transporter 1 (THTR-1). Induction of the mouse THTR-1 (mTHTR-1) mRNA was detectable as early as 1 h at 32.5 degrees C; upon shifting back to 38.5 degrees C, mTHTR-1 transcript was rapidly degraded with a half-life of less than 2 h. Elevation of mTHTR-1 expression was found in DNA damage-induced normal mouse embryonic fibroblast cells, but not in p53(-/-) mouse embryonic fibroblast cells, suggesting that mTHTR-1 induction was p53-dependent. A region within the first intron of the mTHTR-1 gene bound to p53 and conferred the p53-mediated transactivation. Furthermore, increased thiamine transporter activities were found in cells overexpressing mTHTR-1 and under conditions of DNA damage or p53 activation. Our findings indicate that p53 may be involved in maintaining thiamine homeostasis through transactivation of THTR-1.
29. J Pediatr Gastroenterol Nutr. 2001 Jul;33(1):64-9.
Thiamine, riboflavin, pyridoxine, and vitamin C status in premature infants receiving parenteral and enteral nutrition.
Friel JK, Bessie JC, Belkhode SL, Edgecombe C, Steele-Rodway M, Downton G, Kwa PG, Aziz K.
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada. jfriel@morgan.ucs.mun.ca
BACKGROUND: There is a paucity of data about water soluble vitamin status in low birthweight infants. Therefore, the authors' objective was to assess current feeding protocols. METHODS: The authors measured serum concentrations for riboflavin, pyridoxine, and vitamin C and functional assays for thiamine and riboflavin longitudinally in 16 premature infants (birthweight, 1,336 +/- 351 g; gestational age, 30 +/- 2.5 weeks) before receiving nutrition (time 1, 2 +/- 1 days), during supplemental or parenteral nutrition (time 2, 16 +/- 10 days) and while receiving full oral feedings (time 3, 32 +/- 15 days). In plasma, vitamin C was measured colorimetrically, and riboflavin and pyridoxine were measured using high-performance liquid chromatography. The erythrocyte transketolase test as a functional evaluation of thiamine and the erythrocyte glutathione reductase test for riboflavin were measured colorimetrically. RESULTS: At time 1, nutrient intake of vitamins were negligible because infants were receiving intravenous glucose and electrolytes only. Intakes differed between time 2 and time 3 for thiamine (510 +/- 280 and 254 +/- 115 microg. kg-1. d-1, respectively), riboflavin (624 +/- 305 and 371 +/- 193 microg. kg-1. d-1, respectively), and pyridoxine (394 +/- 243 and 173 +/- 85 microg/100 kcal, respectively), but not for vitamin C (32 +/- 17 and 28 +/- 12 mg. kg-1. d-1, respectively). Blood levels at times 1, 2, and 3 were for thiamine (4.9 +/- 2.7%, 3.3 +/- 6.6%, and 4.1 +/- 9% erythrocyte transketolase test, respectively), riboflavin (0.91 +/- 0.31, 0.7 +/- 0.3, 0.91 +/- 0.18 erythrocyte glutathione reductase test, respectively), riboflavin (19.5 +/- 17, 23.3 +/- 8.6, 17.6 +/- 10 ng/mL, respectively), pyridoxine (32 +/- 25, 40 +/- 16, 37 +/- 26 ng/mL, respectively), and vitamin C (5.2 +/- 3, 5 +/- 2.2, 10 +/- 5 microg/mL, respectively) and did not differ at those times. CONCLUSIONS: Current intakes of these vitamins, except for possibly vitamin C, during parenteral and enteral nutrition seem to result in adequate plasma concentrations and normal functional indices.
30. Neurology. 2001 Jun 26;56(12):1727-32.
Painful alcoholic polyneuropathy with predominant small-fiber loss and normal thiamine status.
Koike H, Mori K, Misu K, Hattori N, Ito H, Hirayama M, Sobue G.
Department of Neurology, Nagoya University School of Medicine, Japan.
BACKGROUND: Although polyneuropathy related to chronic alcoholism has been reported frequently, its clinical features and pathogenesis remain to be clarified. OBJECTIVE: To determine the clinicopathologic features and pathogenesis of alcoholic polyneuropathy associated with pain in patients with normal thiamine status, particularly in comparison to beriberi neuropathy. PATIENTS AND METHODS: Clinical, electrophysiologic, and histopathologic findings were assessed in 18 patients with painful alcoholic polyneuropathy and normal thiamine status. RESULTS: Symmetric sensory-dominant polyneuropathy predominantly involving the lower limbs was the major clinical pattern. Painful sensations with or without burning quality represented the initial and major symptom. Progression of symptoms usually was gradual, continuing over months or years. Electrophysiologic and pathologic findings mainly indicated an axonal neuropathy. Densities of small myelinated fibers and unmyelinated fibers were more severely reduced than the density of large myelinated fibers, except in patients with a long history of neuropathic symptoms and marked axonal sprouting. CONCLUSIONS: The clinicopathologic features of painful symptoms and small axon loss are distinct from those of beriberi neuropathy. Sensory-dominant involvement with prominent neuropathic pain is characteristic of alcoholic neuropathy when thiamine deficiency is not involved, supporting the view of direct neurotoxic effect by alcohol or its metabolites.
31. Cochrane Database Syst Rev. 2001;(2):CD001498.
Update of: Cochrane Database Syst Rev. 2000;(2):CD001498.
Thiamine for Alzheimer's disease.
Rodriguez-Martin JL, Qizilbash N, Lopez-Arrieta JM.
Iberoamerican Cochrane Centre, Department of Epidemiology, Hospital de la Santa Creu i Sant Pau, Sant Antoni M feminine Claret, 171, Barcelona, Catalunya, Spain, 08041. jrodriguezma@hsp.santpau.es
BACKGROUND: Vitamin B1 (thiamine) plays an important role in Wernicke-Korsakoff syndrome (a form of amnesia caused by brain damage occurring in long-term alcoholics who rely mainly on alcohol for nutrition). The acute syndrome is normally reversible but may proceed to profound dementia, although its progress can be stopped by a timely injection of a large dose of thiamine. There have been suggestions that thiamine may have a beneficial effect in Alzheimer's disease. OBJECTIVES: The objective of this systematic review is to evaluate the efficacy of thiamine for people with Alzheimer's disease. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Issue 3:2000), the CDCIG Trials Register and other sources were searched for this update in July 2000 using the terms 'alzheimer*', thiamin* and vitamin B1'. In addition bibliographies of published reviews, and conference proceedings were searched and pharmaceutical companies and trials investigators were contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with thiamine was administered for more than a day and compared with placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and the odds ratios (95% CI) or the average differences (95% CI) were estimated. MAIN RESULTS: There are three included studies, but few results were reported that could be included. The cross-over studies did not report results from the first phase. It was not possible to pool any results for a meta-analysis. Nolan 1991 reports results that show no evidence of an effect on MMSE at 3, 6, 9 and 12 months for thiamine compared with placebo for those who completed the trial. Meador 1993a noted that 3/8 on thiamine compared with 6/9 on placebo were worse as measured on the ADAS-Cog at 3 months compared with baseline, but the difference is not statistically significant. Blass 1988 and Nolan 1991 reported that no significant side-effects were noted during the study, and Meador 1993a did not mention side-effects. Blass 1988 noted that 5/16 and Nolan 1991 that 5/15 did not complete the study, but neither mentioned the groups to which these people belonged. REVIEWER'S CONCLUSIONS: It is not possible to draw any conclusions from this review. The number of people included in the studies if less than 50 and the reported results are inadequate.
32. Am J Physiol Gastrointest Liver Physiol. 2001 Jul;281(1):G144-50.
Mechanism of thiamine uptake by human colonocytes: studies with cultured colonic epithelial cell line NCM460.
Said HM, Ortiz A, Subramanian VS, Neufeld EJ, Moyer MP, Dudeja PK.
Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA. hmsaid@uci.edu
Thiamine (vitamin B(1)) is essential for normal cellular functions and growth. Mammals cannot synthesize thiamine and thus must obtain the vitamin via intestinal absorption. The intestine is exposed to a dietary thiamine source and a bacterial source in which the vitamin is synthesized by the normal microflora of the large intestine. Very little is known about thiamine uptake in the large intestine. The aim of this study was, therefore, to address this issue. Our results with human-derived colonic epithelial NCM460 cells as a model system showed thiamine uptake to be 1) temperature- and energy dependent, 2) Na(+) independent, 3) increased with increasing buffer pH from 5 to 8 and after cell acidification but inhibited by amiloride, 4) saturable as a function of concentration, 5) inhibited by thiamine structural analogs but not by unrelated organic cations, and 6) inhibited by modulators of a Ca(2+)/calmodulin-mediated pathway. NCM460 cells and native human colonic mucosa expressed the recently cloned human thiamine transporter THTR-1 (product of the SLC19A2 gene) at both mRNA and protein levels. These results demonstrate for the first time that human NCM460 colonocytes possess a specific carrier-mediated system for thiamine uptake that appears to be under the regulation of an intracellular Ca(2+)/calmodulin-mediated pathway. It is suggested that bacterially synthesized thiamine in the large intestine may contribute to thiamine nutrition of the host, especially toward cellular nutrition of the local colonocytes.
33. Can J Neurol Sci. 2001 May;28(2):134-40.
Biogenic amine metabolites and thiamine in cerebrospinal fluid in heredo-degenerative ataxias.
Botez MI, Young SN.
Department of Medicine, Hotel Dieu Hospital and University of Montreal.
BACKGROUND: The aims of the present study were: i) to measure levels of the dopamine metabolite homovanillic acid (HVA), the serotonin metabolite 5-hydroxindoleacetic acid (5HIAA) and precursor tryptophan, as well as the noradrenaline metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and thiamine in the cerebrospinal fluid (CSF) of patients with Friedreich's ataxia (FA), olivopontocerebellar atrophy (OPCA), and the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSAC), as compared with sex- and age-matched control subjects. PATIENTS AND METHODS: CSF amine related compound levels and thiamine results were compared in 40 FA, 44 OPCA and nine ARSAC patients with those of 94 sex- and age-matched subjects. Neuroimaging (CT scans and single photon emission computed tomographies i.e. SPECT) were carried out in all patients and controls. Genetic studies were conducted on OPCA patients. CSF amine related compounds were measured by high performance liquid chromatography, whereas CSF thiamine levels were measured by a microbiological method. RESULTS: FA patients had significantly lower CSF HVA, 5HIAA and thiamine values than control patients and a trend for lower MHPG levels. In OPCA patients, CSF HVA, MHPG and thiamine values were markedly lower whereas CSF 5HIAA values showed only a trend towards lower levels; in ARSAC patients only thiamine and HVA CSF values were lower than those in control subjects. CONCLUSION: After presenting the relationships between neurochemical findings on one side, the degree of ataxia, the degree of cerebellar atrophy and the SPECT findings on the other, the authors concluded that replacement and neuroprotective clinical trials in these patients would have to include two or three drugs because the neurotransmitter deficiencies are multiple.
34. Nutrition. 2001 Apr;17(4):351-2.
Comment in: Nutrition. 2002 Jan;18(1):118.
Severe metabolic acidosis and heart failure due to thiamine deficiency.
Ozawa H, Homma Y, Arisawa H, Fukuuchi F, Handa S.
Department of Internal Medicine, Tokai University Oiso Hospital, Oiso, Japan.
We report the case of a male patient with severe metabolic acidosis and heart failure caused by thiamine deficiency. He was admitted in August 1998 to the Tokai University Oiso Hospital because of severe dyspnea. The patient was diagnosed with heart failure and metabolic acidosis of unknown causes based on arterial blood gas analysis, chest x ray, and ultrasonic echocardiographic examinations. Our previous experience in treating a patient with thiamine deficiency caused by total parenteral nutrition without thiamine supplementation suggested that this patient was deficient in thiamine. The serum thiamine level was low and the lactate level was high. After intravenous administration of thiamine, the acidosis and heart failure disappeared. Dietary analysis showed that thiamine intake was low (0.32 mg/1000 kcal/d). Thiamine deficiency should be included in the differential diagnosis when encountering cases of heart failure with severe metabolic acidosis, even in developed countries.
35. Int J STD AIDS. 2001 Jun;12(6):407-9.
Severe lactic acidosis and thiamine administration in an HIV-infected patient on HAART.
Arici C, Tebaldi A, Quinzan GP, Maggiolo F, Ripamonti D, Suter F.
Unita Operativa Perativa di Malattie Infettive, Ospedali Riuniti di Bergamo, Italy. aricirm@tin.it
Severe lactic acidosis has been increasingly reported as a potentially fatal complication of HIV treatment. We report on an asymptomatic HIV-infected woman treated with stavudine, lamivudine and indinavir for one year. She was hospitalized because of progressive dispnoea, oedema, cyanosis and severe lactic acidosis. Arterial blood pH was 6.98, bicarbonate 4.4 mmol/l (normal value 22-26), blood lactate: 29.7 mmol/l (normal value <2.2). Hepatic function was normal. She had an impressively rapid response (within a few hours) to empirical treatment with thiamine (100 mg i.v.). No evidence of sepsis or malabsorption were identified and vitamin B1 level was not tested before thiamine infusion. Three months later she was re-started successfully on nelfinavir plus nevirapine. The rapid response to thiamine infusion deserves a careful attention and such an approach should be considered in similar cases as a support treatment of this potentially life-threatening complication of HIV therapy.
36. Blood Cells Mol Dis. 2001 Jan-Feb;27(1):135-8.
Thiamine-responsive megaloblastic anemia syndrome: a disorder of high-affinity thiamine transport.
Neufeld EJ, Fleming JC, Tartaglini E, Steinkamp MP.
Division of Hematology, Children's Hospital, Boston, Massachusetts 02115, USA. ellis.neufeld@tch.harard.edu
Thiamine-responsive megaloblastic anemia (TRMA) syndrome (OMIM No. 249270) comprises a distinctive triad of clinical features: megaloblastic anemia with ringed sideroblasts, diabetes mellitus, and progressive sensorineural deafness. The TRMA gene has been mapped and cloned. Designated "SLC19A2" as a member of the solute carrier gene superfamily, this gene is mutated in all TRMA kindreds studied to date. The product of the SLC19A2 gene is a membrane protein which transports thiamine (vitamin B1) with sub-micromolar affinity. Cells from TRMA patients are uniquely sensitive to thiamine depletion to the nanomolar range, while pharmacologic doses of vitamin B1 ameliorate the anemia and diabetes. Here we review the current status of studies aimed at understanding the pathophysiology of this unique transport defect. Copyright 2001 Academic Press.
37. Clin Nephrol. 2000 May;53(5):400-3.
Efficacy of hemodiafiltration in a child with severe lactic acidosis due to thiamine deficiency.
Pela I, Seracini D, Lavoratti GC, Sarti A.
Paediatric Clinic 1, Paediatrics Department, University of Florence, Italy.
We report the case of a child in whom severe lactic acidosis (LA) and hyperammonemia developed after twenty days of total parenteral nutrition (TPN) for diffuse esophageal damage due to caustic ingestion. The revision of TPN preparation revealed that thiamine was never included and the hypothesis of thiamine deficiency was later confirmed measuring the serum thiamine level. Because severe metabolic acidosis the dialytic treatment with hemodiafiltration (HDF) and bicarbonate infusion were performed: the patient very quickly recovered with dramatic reestablishment of the acid-basic balance. Thiamine administration restored lactate metabolism. We emphasize that HDF is a useful and prompt treatment for LA to get over the critical phase of neurological and cardiological damage.
38. Am J Gastroenterol. 2001 Mar;96(3):864-8.
Thiamine treatment of chronic hepatitis B infection.
Wallace AE, Weeks WB.
Department of Psychiatry and Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA.
OBJECTIVE: Chronic hepatitis B is an international health concern that causes cirrhosis, hepatocellular carcinoma, liver failure, and death. Current treatment options are expensive and associated with side effects; however, indirect evidence suggests a relationship between relative thiamine deficiency and chronic hepatitis B infection. METHODS: The authors present three case studies wherein multiple crossovers of daily thiamine administration were used to evaluate a hypothesized association between thiamine treatment and aminotransferase levels. RESULTS: In each case study, thiamine administration was associated with reduction in aminotransferase levels and the fall of HBV DNA to undetectable levels. Analyses by t test demonstrated a statistically significant reduction in aminotransferase levels in all three cases. CONCLUSIONS: The relationship between thiamine administration and chronic hepatitis B infection warrants further study. If proven effective in reducing liver damage or inducing remission of the hepatitis B virus in larger trials, thiamine will offer obvious advantages over the current treatments for chronic viral hepatitis B infection.
39. J Biochem (Tokyo). 2001 Apr;129(4):543-9.
Suppression of the accumulation of triosephosphates and increased formation of methylglyoxal in human red blood cells during hyperglycaemia by thiamine in vitro.
Thornalley PJ, Jahan I, Ng R.
Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester CO4 3SQ, Essex, UK. thorp@essex.ac.uk
The accumulation of triosephosphates and the increased formation of the potent glycating agent methylglyoxal in intracellular hyperglycaemia are implicated in the development of diabetic complications. A strategy to counter this is to stimulate the anaerobic pentosephosphate pathway of glycolysis by maximizing transketolase activity by thiamine supplementation, with the consequent consumption of glyceraldehyde-3-phosphate and increased formation of ribose-5-phosphate. To assess the effect of thiamine supplementation on the accumulation of triosephosphates and methylglyoxal formation in cellular hyperglycaemia, we incubated human red blood cell suspensions (50% v/v) in short-term culture with 5 mM glucose and 50 mM glucose in Krebs-Ringer phosphate buffer at 37 degrees C as models of cellular metabolism under normoglycaemic and hyperglycaemic conditions. In hyperglycaemia, there is a characteristic increase in the concentration of the triosephosphate pool of glycolytic intermediates and a consequent increase in the concentration and metabolic flux of the formation of methylglyoxal. The addition of thiamine (50-500 microM) increased the activity of transketolase, decreased the concentration of the triosephosphate pool, decreased the concentration and metabolic flux of the formation of methylglyoxal, and increased the concentration of total sedoheptulose-7-phosphate and ribose-5-phosphate. Biochemical changes implicated in the development of diabetic complications were thereby prevented. This provides a biochemical basis for high dose thiamine therapy for the prevention of diabetic complications.
40. Ann Fr Anesth Reanim. 2001 Jan;20(1):40-3.
[Postoperative encephalopathies: thiamine deficiency, an unrecognized etiology]
[Article in French]
Vidal S, Andrianjatovo JJ, Dubau B, Winnock S, Maurette P.
Departement d'anesthesie-reanimation III, CHU Pellegrin, 33076 Bordeaux, France.
We report the case of a patient who experienced a postoperative Wernicke encephalopathy 8 days after a left hepatectomy performed for metastasis related to a rectal cancer. During the six months before surgery the patient lost 10 kg of weight (15%). Moreover, in the postoperative period the patient received exclusively 5% dextrose solution intravenously. On the 8th postoperative day, an alteration of consciousness, a vertical nystagmus and an ataxia led to consider the diagnosis of thiamine deficiency that was then established by the decrease in the transcetolase activity of the red blood cells. Vitamin B1 supply improved the clinical status rapidly and completely. This observation allows to review aetiologies and clinical forms of thiamine shortage. In addition, it stresses the detection of exposed patients and the prevention methods.
41. Am J Kidney Dis. 2001 Feb;37(2):427-30.
Chorea induced by thiamine deficiency in hemodialysis patients.
Hung SC, Hung SH, Tarng DC, Yang WC, Huang TP.
Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Thiamine deficiency is mainly encountered in alcoholics or food faddists, but it may complicate chronic dialysis because of low intake and accelerated loss of thiamine in dialysis patients. We report here 2 hemodialysis (HD) patients who developed chorea induced by thiamine deficiency. We propose that thiamine deficiency, with a consequent dysfunction of the basal ganglia, may induce chorea in HD patients.
42. Eur Neurol. 2001;45(1):34-7.
Thiamine-responsive acute neurological disorders in nonalcoholic patients.
Merkin-Zaborsky H, Ifergane G, Frisher S, Valdman S, Herishanu Y, Wirguin I.
Department of Neurology, Soroka University Medical Center, Goldman Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Wernicke's encephalopathy (WE) is most commonly associated with alcoholism, although other causes have also been implicated. In the years 1994-1997, 9 patients with no history of alcohol abuse presented with acute signs of ophthalmoplegia or nystagmus and ataxia which resolved within 48 h after intravenous thiamine. There were 7 women and 2 men aged 17-57 (7 below the age of 30). Precipitating events included vomiting 2, drastic weight-reducing diet 2, renal colic in a postpartum woman 1, colonic surgery 2 and chronic hemodialysis 1. In 2 patients there was no obvious precipitating event but their history was suggestive of a genetic predisposition. Mental changes were slight or absent in all patients and all of them made good functional recovery. These cases suggest that the diagnosis of WE should be considered more often in nonalcoholics in various clinical settings. Copyright 2001 S. Karger AG, Basel
43. Ophthalmic Genet. 2000 Dec;21(4):243-50.
Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy.
Meire FM, Van Genderen MM, Lemmens K, Ens-Dokkum MH.
Department of Pediatric Ophthalmology, Ghent University Hospital, Ghent, Belgium.
Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive disease in which the active thiamine uptake into cells is disturbed. The molecular basis underlying the disorder has been related to mutations in the gene SLC19A2 on chromosome 1q23.3 that encodes a functional thiamine transporter. The protein is predicted to have 12 transmembrane domains. TRMA is characterized by sensorineural deafness, diabetes mellitus, megaloblastic anemia, and cardiomyopathy. Optic nerve atrophy and retinal dystrophy have been reported in a small number of patients. We report a 15-year-old girl with TRMA and cone-rod dystrophy and confirm that retinal dystrophy may form part of the syndrome. Differential diagnosis of syndromes with deafness, diabetes mellitus, and optic nerve atrophy or retinal dystrophy are discussed. The authors suggest that ERG be performed in all patients with TRMA.
44. Rev Med Interne. 2000 Nov;21(11):993-7.
[Pericardial extravasation as an indicator of congestive heart failure due to thiamine deficiency in a young adult]
[Article in French]
Hurreesing C, Babuty D, Fauchier L, d'Alteroche L, Montout M, Poret P, Cosnay P.
Service de cardiologie B, hopital Trousseau, Tours, France.
INTRODUCTION: Thiamine (B1) deficiency is one of the classical causes of congestive heart failure. Although in the western world and in other developed regions this disorder is generally associated with chronic alcoholism, it may also only occur as a result of a deficient diet. EXEGESIS: A young patient was admitted for electrocardiographic examination, and pericardial extravasation was recorded. The etiological assessment showed a case of congestive heart failure due to thiamine (B1) deficiency. A hemodynamic examination and investigation of thiamine blood levels confirmed this diagnosis. The patient's health status improved following thiamine administration, with complete and rapid regression of symptoms of congestive heart failure. CONCLUSION: Although cardiomyopathic beriberi is infrequent, it should systematically be taken into account in the etiology of congestive heart failure. The present study also notes that a dietary thiamine deficiency is uncommon, but should nevertheless be considered when other symptoms of denutrition are present.
45. Przegl Lek. 2000;57(7-8):369-73.
[The effect of cocarboxylase treatment on erythrocyte transketolase and blood thiamine in patients with end stage renal disease undergoing maintenance hemodialysis]
[Article in Polish]
Pietrzak I, Czarnecki R, Baczyk K, Mlynarczyk M, Kaczmarek M.
Klinika Nefrologii, Instytutu Chorob Wewnetrznych, Akademii Medycznej im. K. Marcinkowskiego w Poznaniu.
The depressed ETKA in ESRD patients is supposed to be caused and/or aggravated by several factors among which the diminished content of thiamine in blood and/or disturbances of thiamine utilization seem to play the major role. This role stems from the fact that thiamine acts as the cofactor of transketolase. In order to check the therapeutic significance of this relationship we introduced the thiamine pyrophosphoric acid ester chloride (Cocarboxylasum-CC) administration in 25 patients (mHD + CC). Immediately after each HD performance CC was given i.v. during 12 weeks in a doses of 5 mg/kg b.w., 3 times a week. The blood for ETKA value, free and total thiamine in plasma and erythrocytes, as well as, the total protein and albumins/globulins index investigation was drawn before, after 6 and 12 weeks of CC administration, and 3 months after cessation of this therapy. In 10 patients, on maintenance HD nontreated by CC (mHD), the blood was drawn at the same time intervals. Normal values we obtained from 15 healthy volunteers. For ETKA evaluation photocolorimetric method was used, thiamine content in blood was estimated by fluorimetric method. At the beginning of the study the mean value of ETKA, in two examined groups, was found statistically decreased (p < 0.01) when compared with normals. Mean values of thiamine in plasma and erythrocytes were lower but did not differ significantly from those in normals. After 6 weeks of CC administration ETKA value increased, but only after 12 weeks it increased significantly (p < 0.01), reaching normal value. On the other hand, striking increase in plasma thiamine and erythrocyte thiamine levels was observed after 6 weeks of CC administration already (p < 0.01). Three months after cessation of CC administration significant decrease in ETKA value and thiamine level in blood was observed (p < 0.01). ETKA returned to lower value than in normals even in the presence of still high thiamine levels in blood. In mHD patients nontreated by CC the ETKA value and thiamine levels in blood did not change significantly during all periods of study. The nutritional status assessed by total protein and albumins/globulins index did not change in both groups through the study. We conclude, the administration of high doses of CC to ESRD patients on maintenance hemodialysis HD was successful in terms of increasing ETKA value and thiamine levels in blood without any side effects. Thus, supplementation with large doses of CC deserves further study because it promises to be another adjunct in the treatment of potential thiamine deficiency and metabolic disturbances in the course of dialysotherapy.
46. Am J Med Sci. 2000 Oct;320(4):278-80.
Unilateral internuclear ophthalmoplegia and recovery with thiamine in Wernicke syndrome.
Kumar PD, Nartsupha C, West BC.
Department of Medicine, Huron Hospital/Cleveland Clinic Health System, Ohio 44112, USA. ponondileep@hotmail.com
Internuclear ophthalmoplegia is usually caused by multiple sclerosis, tumors, or vascular lesions of the brain stem. We report a patient with Wernicke syndrome who presented with a right-sided internuclear ophthalmoplegia. He recovered completely with intravenous thiamine (vitamin B1). There were no lesions in the magnetic resonance image (MRI) of the brain, suggesting a derangement at the cellular level as the cause.
47. Med Hypotheses. 2000 Jul;55(1):88-90.
Thiamine supplementation to prevent induction of low birth weight by conventional therapy for gestational diabetes mellitus.
Bakker SJ, ter Maaten JC, Gans RO.
Department of Internal Medicine, University Hospital Groningen, The Netherlands. s.j.i.bakker@int.azg.nl
Conventional treatment for gestational diabetes mellitus increases the proportion of infants born with a low birth weight, a risk factor for cardiovascular disease and diabetes mellitus in later life. Thiamine supplementation during pregnancy may be shown to be a safe preventive measure. During pregnancy, approximately 50% of the women develop a biochemical thiamine deficiency, whereas the thiamine status falls, but remains within normal limits, in most other women. Thiamine is essential for glucose oxidation, insulin production by pancreatic beta-cells and cell growth. It is therefore likely that thiamine supplementation in pregnant women not only improves their glucose tolerance but also stimulates the intra-uterine growth, thereby preventing a low birth weight to ensue from conventional therapy which only improves glucose tolerance.
48. Acad Emerg Med. 2000 Oct;7(10):1156-9.
Low plasma thiamine levels in elder patients admitted through the emergency department.
Lee DC, Chu J, Satz W, Silbergleit R.
Department of Emergency Medicine, North Shore University Hospital, Manhasset, NY 11030, USA. dlee@nshs.edu
OBJECTIVES: To determine the prevalence of thiamine deficiency in a high-risk group of elder emergency department (ED) patients who reside in nursing homes and need admission to the hospital, and to determine the effect of patients' diets on this prevalence. METHODS: This was an observational pilot study of 75 consecutive ED patients aged 65 years or older who lived in a nursing home and were admitted to the hospital. Plasma thiamine levels were measured by high-pressure liquid chromatography on serum samples collected within 24 hours of hospital admission. Nursing home records were reviewed to determine whether patients received nutritional supplementation or enteral tube feedings. RESULTS: Seventy patients participated and had a mean plasma thiamine level of 27.3 microg/dL (95% CI = 20.2 to 34.4). Fourteen percent (n = 10, 95% CI = 8% to 24%) were thiamine-deficient (<10 microg/dL). Patients not receiving dietary supplements or tube feedings (n = 26) had lower mean thiamine levels (20.3 microg/dL, 95% CI = 12.7 to 27.9) and were thiamine-deficient more often (27%) than patients receiving dietary support (n = 44, 31.5 microg/dL, 95% CI = 24.7 to 38.3, 7% thiamine-deficient). CONCLUSIONS: Elder nursing home patients seen in the ED and admitted to the hospital are frequently thiamine-deficient. Empiric thiamine supplementation is often used in the ED for other high-risk patients, such as alcoholic individuals, and may be appropriate for high-risk elder patients. Further research is needed to determine whether thiamine supplementation in these patients can improve their clinical outcomes.
49. J Med Genet. 2000 Sep;37(9):669-73.
A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I.
Scharfe C, Hauschild M, Klopstock T, Janssen AJ, Heidemann PH, Meitinger T, Jaksch M.
Department of Medical Genetics, Klinikum Innenstadt, Ludwig-Maximilians- University, Munich, Germany.
The thiamine transporter gene SLC19A2 was recently found to be mutated in thiamine responsive megaloblastic anaemia with diabetes and deafness (TRMA, Rogers syndrome), an early onset autosomal recessive disorder. We now report a novel G1074A transition mutation in exon 4 of the SLC19A2 gene, predicting a Trp358 to ter change, in a girl with consanguineous parents. In addition to the typical triad of Rogers syndrome, the girl presented with short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Both muscle and skin biopsies were obtained before high dose thiamine supplementation. While no mitochondrial abnormalities were seen on morphological examination of muscle, biochemical analysis showed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. In the patient's fibroblasts, the supplementation with high doses of thiamine resulted in restoration of complex I activity. In conclusion, we provide evidence that thiamine deficiency affects complex I activity. The clinical features of TRMA, resembling in part those found in typical mitochondrial disorders with complex I deficiency, may be caused by a secondary defect in mitochondrial energy production.
50. Proc Soc Exp Biol Med. 2000 Sep;224(4):246-55.
Thiamine intestinal transport and related issues: recent aspects.
Rindi G, Laforenza U.
Institute of Human Physiology, University of Pavia, Pavia, Italy.
In the intestinal lumen thiamine is in free form and very low concentrations. Absorption takes place primarily in the proximal part of the small intestine by means of a dual mechanism, which is saturable at low (physiological) concentrations and diffusive at higher. Thiamine undergoes intracellular phosphorylation mainly to thiamine pyrophosphate, while at the serosal side only free thiamine is present. Thiamine uptake is enhanced by thiamine deficiency, and reduced by thyroid hormone and diabetes. The entry of thiamine into the enterocyte, as evaluated in brush border membrane vesicles of rat small intestine in the absence of H+ gradient, is Na+- and biotransformation-independent, completely inhibited by thiamine analogs and reduced by ethanol administration and aging. The transport involves a saturable mechanism at low concentrations of vitamin and simple diffusion at higher. Outwardly oriented H+ gradients enhance thiamine transport, whose saturable component is a Na+-independent electroneutral uphill process utilizing energy supplied by the H+ gradient, and involving a thiamine/ H+ 1:1 stoichiometric exchange. The exit of thiamine from the enterocyte, as evaluated in basolateral membrane vesicles, is Na+-dependent, directly coupled to ATP hydrolysis by Na+-K+-ATPase, and inhibited by thiamine analogs. Transport of thiamine by renal brush border membrane vesicles is similar to the intestinal as far as both H+ gradient influence and specificity are concerned. In the erythrocyte thiamine transport is a Na+-independent, electroneutral process yet with two components: saturable, prevailing at low thiamine concentrations, and diffusive at higher. The saturable (specific) component is missing in patients of the rare disease known as thiamine-responsive megaloblastic anaemia (TRMA), producing a general disturbance of thiamine transport up to thiamine deficiency. The TRMA gene is located in chromosome 1q23.3. Recently, the thiamine transporter has been cloned: it is a protein of 497 amino acid residues with high homology with the reduced-folate transporter.
51. Eur J Clin Pharmacol. 2000 Jun;56(3):251-7.
High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfontiamine.
Frank T, Bitsch R, Maiwald J, Stein G.
Institute of Nutrition, Department of Human Nutrition, Friedrich-Schiller-University, Jena, Germany. Thomas.Frank@uni-jena.de
OBJECTIVE: The influence of either orally administered S-benzoylthiamine-O-monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was tested in a randomised, two-group comparison study in 20 end-stage renal disease (ESRD) patients. Main outcome measures were the pharmacokinetics of thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase activity, its activation coefficient (alpha-ETK) and the TDP concentration in erythrocytes. METHODS: After ingestion of a single dose of either 100 mg thiamine nitrate (corresponding to 305 micromol thiamine) or 100 mg benfotiamine (corresponding to 214 micromol thiamine), the blood levels of thiamine phosphate esters were analysed by means of high-performance liquid chromatography for a 24-h period. The TDP concentration in erythrocytes was calculated using the haematocrit and TDP concentration in blood. Erythrocyte transketolase activity and alpha-ETK were measured before and 10 h after administration. The pharmacokinetics of TDP in blood were compared with healthy subjects of other studies retrieved from database query. RESULTS: Regarding the blood concentrations of TDP, the patients with ESRD had a 4.3 times higher area under the concentration time curve after benfotiamine administration than after thiamine nitrate. After benfotiamine administration, the peak plasma concentration of TDP exceeded that in healthy subjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration in erythrocytes increased from 158.7+/-30.9 ng/ml initially to 325.8+/-50.9 ng/ml after administration of benfotiamine and from 166.2+/-51.9 ng/ml to 200.5+/-50.0 ng/ml after thiamine nitrate administration. The ratio between the maximum erythrocyte TDP concentration and basal concentration was 2.66+/-0.6 in the benfotiamine group and 1.44+/-0.2 in the group receiving thiamine nitrate (P < 0.001). After 24 h, it was 2.11+/-0.4 and 1.23+/-0.2, respectively. The transketolase activity increased from 3.54+/-0.7 microkat/l initially to 3.84+/-0.6 microkat/l after benfotiamine intake (P = 0.02) and from 3.71+/-0.8 microkat/l to 4.02+/-0.7 microkat/l after thiamine nitrate intake (P = 0.08). Likewise, alpha-ETK decreased from initially 1.10+/-0.07 to 1.04+/-0.04 (P = 0.04) and from 1.12+/-0.05 to 1.08+/-0.06 (P = 0.09). After 24 h, the phosphorylation ratio in whole blood decreased from 12.9+/-6.9 initially to 5.6+/-3.2 after benfotiamine administration (P = 0.02) and from 13.5+/-7.3 to 9.0+/-4.8 (P = 0.03) after administration of thiamine nitrate. No correlation between erythrocyte TDP concentration and transketolase activity and/or alpha-ETK was observed in ESRD patients, either before or 10 h after administration. CONCLUSION: Compared with thiamine nitrate, the oral administration of benfotiamine leads to higher TDP concentrations in erythrocytes accompanied with a significant improvement of the erythrocyte transketolase activity in ESRD patients.
52. Vet Hum Toxicol. 2000 Aug;42(4):236-7.
Effect of thiamine hydrochloride on lead induced lipid peroxidation in rat liver and kidney.
Senapati SK, Dey S, Dwivedi SK, Patra RC, Swarup D.
Division of Medicine, Indian Veterinary Research Institute, Izatnagar.
Thiamine hydrochloride was studied on lead-induced endogenous lipid peroxidation in rat hepatic and renal tissues following po doses of 2.73 mg lead/kg bw for 6 w. Simultaneous use of 25 mg thiamine hydrochloride/kg bw po reduced lead accumulation in liver and kidneys. There were significant decreases in endogenous lipid peroxide in liver and kidney from thiamine hydrochloride-treated rats. Histopathological lesions in thiamine-treated livers and kidneys were milder in comparison to lesions in untreated Pb-exposed animals. This indicates the prophylactic potential of thiamine for lead-induced lipid peroxidation.
53. Anticancer Res. 2000 May-Jun;20(3B):2245-8.
Population thiamine status and varying cancer rates between western, Asian and African countries.
Boros LG.
UCLA School of Medicine, Harbor-UCLA Research and Education Institute, Torrance 90502, USA. boros@gcrc.humc.edu
The role of food supplements in the form of vitamins has not been extensively investigated in relation to varying cancer rates between populations of different geographical regions. New data indicate that thiamine (vitamin B1), a common food supplement in Western food products, is directly involved in nucleic acid ribose synthesis of tumor cells in its biologically activated form through the non-oxidative transketolase catalyzed pentose cycle reaction. Whether thiamine plays a role in increased cancer rates in the Western World by enhancing tumor cell proliferation, while increased consumption of thiaminase rich food limiting thiamine availability protects against common malignancies in Asia and Africa has not been evaluated. In the Western World, thiamine is a popular vitamin supplement in the form of tablets and it is also added to basic food items such as milled flour, cereals, peanut butter, refreshment drinks and pastas. On the contrary, thiaminase, the natural thiamine-degrading enzyme, is abundantly present in raw and fermented fish, certain vegetables and roasted insects consumed primarily in Africa and Asia. Excess thiamine supplementation in common food products may contribute to the increased cancer rates of the Western World.
54. Am J Clin Nutr. 2000 Aug;72(2 Suppl):598S-606S.
Effect of physical activity on thiamine, riboflavin, and vitamin B-6 requirements.
Manore MM.
Food and Nutrition Laboratory, the Department of Family Resources and Human Development, Arizona State University, Tempe, AZ 85212, USA. melinda.manore@asu.edu
Because exercise stresses metabolic pathways that depend on thiamine, riboflavin, and vitamin B-6, the requirements for these vitamins may be increased in athletes and active individuals. Theoretically, exercise could increase the need for these micronutrients in several ways: through decreased absorption of the nutrients; by increased turnover, metabolism, or loss of the nutrients; through biochemical adaptation as a result of training that increases nutrient needs; by an increase in mitochondrial enzymes that require the nutrients; or through an increased need for the nutrients for tissue maintenance and repair. Biochemical evidence of deficiencies in some of these vitamins in active individuals has been reported, but studies examining these issues are limited and equivocal. On the basis of metabolic studies, the riboflavin status of young and older women who exercise moderately (2.5-5 h/wk) appears to be poorer in periods of exercise, dieting, and dieting plus exercise than during control periods. Exercise also increases the loss of vitamin B-6 as 4-pyridoxic acid. These losses are small and concomitant decreases in blood vitamin B-6 measures have not been documented. There are no metabolic studies that have compared thiamine status in active and sedentary persons. Exercise appears to decrease nutrient status even further in active individuals with preexisting marginal vitamin intakes or marginal body stores. Thus, active individuals who restrict their energy intake or make poor dietary choices are at greatest risk for poor thiamine, riboflavin, and vitamin B-6 status.
55. Muscle Nerve. 2000 Jul;23(7):1069-75.
Mitochondrial myopathy and familial thiamine deficiency.
Sato Y, Nakagawa M, Higuchi I, Osame M, Naito E, Oizumi K.
First Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan. y-sato@ktarn.or.jp
We studied two siblings with a mitochondrial myopathy, familial thiamine deficiency, and an A3243G mutation of the mitochondrial DNA (mtDNA). The elder brother (patient 1, now 36 years old) developed myopathy and beriberi heart at 20 years of age. Thiamine therapy resolved the cardiac symptoms and hyperpyruvicemia and improved the myopathy. The younger brother presented aged 19 years with a myopathy (patient 2, now 35 years old). Thiamine deficiency was present in the siblings and parents, and ragged-red fibers (RRFs) were noted in muscle biopsies from the siblings. Analysis 17 years later demonstrated thiamine malabsorption and an A3243G mutation of the mtDNA in both siblings and their mother, progressive myopathy, and an increased number of RRFs and elevated serum CKMB activity in patient 1. Thiamine treatment decreased the serum concentrations of lactate and pyruvate in patient 2, but not patient 1. The role of thiamine in mitochondrial dysfunction caused by an electron transfer disorder in the setting of A3243G mtDNA mutation is discussed. Copyright 2000 John Wiley & Sons, Inc.
56. Hum Mutat. 2000;16(1):37-42.
The spectrum of mutations, including four novel ones, in the thiamine-responsive megaloblastic anemia gene SLC19A2 of eight families.
Raz T, Labay V, Baron D, Szargel R, Anbinder Y, Barrett T, Rabl W, Viana MB, Mandel H, Baruchel A, Cayuela JM, Cohen N.
Department of Genetics, Tamkin Human Molecular Genetics Research Facility, Technion-Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Thiamine responsive megaloblastic anemia (TRMA) is an autosomal recessive disorder with a triad of symptoms: megaloblastic anemia, deafness, and non-type 1 diabetes mellitus. Occasionally, cardiac abnormalities and abnormalities of the optic nerve and retina occur as well. Patients with TRMA often respond to treatment with pharmacological doses of thiamine. Recently, mutations were found in patients with TRMA in a thiamine transporter gene (SLC19A2). We here describe the mutations found in eight additional families. We found four novel mutations and three that were previously described. Of the novel ones, one is a nonsense mutation in exon 1 (E65X), two are missense mutations in exon 2 (S142F, D93H), and another is a mutation in the splicing donor site at the 5' end of intron 4 (C1223+1G>A). We also summarize the state of knowledge on all mutations found to date in TRMA patients. SLC19A2 is the first thiamine transporter gene to be described in humans. Reviewing the location and effect of the disease causing mutations can shed light on the way the protein functions and suggest ways to continue its investigation. Copyright 2000 Wiley-Liss, Inc.
57. Eur J Paediatr Neurol. 2000;4(3):115-7.
Outcome of thiamine treatment in a child with Leigh disease due to thiamine-responsive pyruvate dehydrogenase deficiency.
Di Rocco M, Lamba LD, Minniti G, Caruso U, Naito E.
II Paediatric Division, Gaslini Institute, Genoa, Italy.
We describe a child with severe psychomotor retardation, peripheral neuropathy and bilateral abnormal signal in basal ganglia on magnetic resonance imaging, consistent with Leigh disease. Fibroblast pyruvate dehydrogenase assayed with routine method was normal. However, because of neurological improvement after treatment with thiamine, pyruvate dehydrogenase activity was studied again with thiamine pyrophosphate concentration adjusted to the normal human tissue level and found to be deficient. We report here on diagnostic difficulties and clinical follow-up of this patient.
58. JPEN J Parenter Enteral Nutr. 2000 May-Jun;24(3):154-8.
Thiamine deficiency in children with congenital heart disease before and after corrective surgery.
Shamir R, Dagan O, Abramovitch D, Abramovitch T, Vidne BA, Dinari G.
Division of Pediatric Gastroenterology and Nutrition, Schneider Children's Medical Center of Israel. shamirr@netvision.net.il
BACKGROUND: Malnutrition is common in children with congenital heart disease, while thiamine deficiency (TD) is common in malnutrition, in critically ill children, and in adults with congestive heart failure treated with loop diuretics. Our goal was to determine whether children with congenital heart disease had TD and whether treatment with loop diuretics is related to TD in these patients. METHODS: Twelve children with ventricular septal defect (VSD) treated with furosemide, and 10 children with tetralogy of Fallot (TOF) referred for corrective surgery were consecutively enrolled into a prospective study. Data were collected 24 hours before surgery and 5 days after surgery for nutrition evaluation, medications used, anthropometric measurements, and laboratory markers of malnutrition. Thiamine and pyridoxine deficiencies were evaluated using activated enzyme assays. RESULTS: Seven children (32% of patients) did not meet the recommended daily allowance (RDA) for calories and 18% of patients did not meet the RDA for thiamine intake. Anthropometric measurements were low in both groups, more so in those with VSD, although the difference did not reach statistical significance. Overall, 18% (1/12 with VSD and 3/10 with TOF) of children with congenital heart disease had thiamine deficiency before surgery. Three of the four children with TD had adequate intake of thiamine. Six children (27%) had TD 5 days postsurgery (3 children with VSD and 3 children with TOF). CONCLUSIONS: TD is common in children with congenital heart disease (CHD) referred for corrective surgery both before and after surgery. Our results suggest that neither diuretic treatment nor malnutrition can fully explain the development of TD in these children.
59. J Nutr Health Aging. 2000;4(2):69-71.
Diuretic use: a risk for subclinical thiamine deficiency in elderly patients.
Suter PM, Haller J, Hany A, Vetter W.
Medical Policlinic, Division of Hypertension, University Hospital, Ramistrasse 100, CH 8091 Zurich, Switzerland. polpms@usz. unizh.ch
Long term diuretic therapy represents one central pharmacologic therapy of heart insufficiency and hypertension. Diuretics lead not only to an increased urinary excretion of electrolytes but also of water soluble vitamins. In this prospective study we evaluated the effect of hospitalization on the overall biochemical vitamin status in subjects older than 50 years (n=149, mean +/- SD age 70 +/- 10 years). Vitamin nutriture and other parameters were assessed at admission and discharge (duration of the hospitalization 19 +/- 1 day). Only vitamin B1 nutriture worsened during the hospitalization and in a multivariate procedure the only significant predictor of the change in the vitamin B1 nutriture was the use of diuretics during the hospitalization (F=4.06, p < 0.001). The changes in the ETK (erythrocyte transketolase activity in whole blood) and a-ETK (ETK activity coefficient) during the hospital stay correlated with the cumulative dosage of furosemide adjusted for the duration of the therapy (r = 0.36, p < 0.001 and r = - 0.28, p > 0.03). Our data suggest that hospitalized elderly are at increased risk for vitamin B1 deficiency especially when on a diuretic treatment. It is possible that a low dose thiamine supplementation my help to prevent the development of a subclinical wet-beriberi in older subjects on diuretics.
60. Ann N Y Acad Sci. 2000 Apr;903:353-6.
Vascular endothelium is a site of free radical production and inflammation in areas of neuronal loss in thiamine-deficient brain.
Calingasan NY, Gibson GE.
Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, New York 10605, USA.
Free radical production in vascular endothelial cells and inflammatory responses in perivascular microglia accompany the selective neuronal death induced by TD. Lipid peroxidation and tyrosine nitration occur in neurons within susceptible areas. Thus, region- and cell-specific oxidative stress contributes to selective neurodegeneration during TD. These data are consistent with the hypothesis that in TD, vascular factors constitute a critical part of a cascade of events leading to increases in blood-brain barrier permeability to nonneuronal proteins and iron, leading to inflammation and oxidative stress. Inflammatory cells may release deleterious compounds or cytokines that exacerbate the oxidative damage to metabolically compromised neurons. Similar mechanisms may operate in the pathophysiology of neurodegenerative diseases in which vascular factors, inflammation and oxidative stress are implicated including AD.
61. J Intern Med. 2000 May;247(5):597-600.
Reduced thiamine phosphate, but not thiamine diphosphate, in erythrocytes in elderly patients with congestive heart failure treated with furosemide.
Hardig L, Daae C, Dellborg M, Kontny F, Bohmer T.
Department of Medicine, Section of Cardiology, Sahlgrenska University Hospital/Ostra, Goteborg, Sweden.
OBJECTIVES: To measure the concentrations of thiamine and thiamine esters by high-pressure liquid chromatography (HPLC) in elderly patients treated with furosemide for heart failure and in a control group. DESIGN: A cross-sectional study of blood thiamine and thiamine ester concentrations. SUBJECTS: Forty-one patients admitted to hospital for heart failure and 34 elderly living at home. No vitamin supplementation was allowed. RESULTS: Compared with the healthy controls, furosemide-treated patients had significantly reduced whole blood thiamine phosphate (TP; 4.4 +/- 2.2 vs. 7.6 +/- 2.0 nmol L-1) and thiamine diphosphate (TPP; 76 +/- 21.5 vs. 91 +/- 19.8 nmol L-1) (mean +/- SD). When the thiamine concentrations were related to the haemoglobin concentrations, which were reduced in the heart failure patients, the levels of TP (nmol g-1 Hb) were 0.38 +/- 0.26 vs. 0.54 +/- 0.17 (P < 0.0001), and of TPP were 6.35 +/- 1.76 vs. 6.37 +/- 1.29 (P = 0.95). There were no differences in T and TP concentrations in plasma between the two groups. CONCLUSIONS: The elderly patients with heart failure treated with furosemide have not reduced the storage form of thiamine, TPP, but only TP. This change is most likely not an expression of a thiamine deficiency, but rather of an altered metabolism of thiamine, which is not understood at present.
62. Cochrane Database Syst Rev. 2000;(2):CD001498.
Update in: Cochrane Database Syst Rev. 2001;(2):CD001498.
Thiamine for Alzheimer's disease.
Rodriguez-Martin JL, Lopez-Arrieta JM, Qizilbash N.
Departamento de Psicobiologia, Universidad Nacional de Educacion a Distancia, Ciudad Universitaria s/n, PO Box 60148, Madrid, Spain, 28040. jrodriguez@meridian.es
BACKGROUND: Vitamin B1 (thiamine) plays an important role in Wernicke-Korsakoff syndrome (a form of amnesia caused by brain damage occurring in long-term alcoholics who rely mainly on alcohol for nutrition). The acute syndrome is normally reversible but may proceed to profound dementia, although its progress can be stopped by a timely injection of a large dose of thiamine. There have been suggestions that thiamine may have a beneficial effect in Alzheimer's disease. OBJECTIVES: The objective of this systematic review is to evaluate evidence of the effect of thiamine for Alzheimer's disease. SEARCH STRATEGY: The Cochrane Controlled Trials Register and the CDCIG Register were searched using the terms 'thiamine*, alzheimer* and vitamin* B1'. Other sources were also searched. SELECTION CRITERIA: All unconfounded, double-blind, randomized trials in which treatment with thiamine was administered for more than a day and compared to placebo in patients with dementia of the Alzheimer's type. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers, pooled if appropriate and possible, and the pooled odds ratios (95% CI) or the average differences (95% CI) were estimated. No intention-to-treat data were available to be used. MAIN RESULTS: Few data were available for review. The data were compatible with thiamine producing harm, no change or improvement. For measures of cognition, the effect of thiamine was non-significantly worse than placebo on the Mini Mental State Examination score (0-30; high=good) at 12 months: WMD -4.3 (95% CI: -14.4 - +5.8) and at time points 3, 6 and 9 months. Change from baseline analyses showed placebo to be significantly better than thiamine at all time points beyond three months; WMD -4.8 (95% CI: -6.0 to -3.6) at 12 months. There was no statistically significant difference in the test of Verbal Fluency and the Boston Naming Test. These analyses were based only on those who completed the study and not on intention-to-treat analyses. There were no results presented for withdrawal by treatment group. Data on measures of functional autonomy, behaviour, quality of life, dependency, or effect on carer were not available. REVIEWER'S CONCLUSIONS: This review finds no evidence that thiamine is a useful treatment for the symptoms of Alzheimer's disease. The data are so poor and sparse that it is difficult to state almost anything of its effect in Alzheimer's disease. Thiamine cannot be recommended for patients with Alzheimer's disease.
63. Age Ageing. 2000 Mar;29(2):111-6.
Comment in: Age Ageing. 2000 Mar;29(2):99-101.
Is thiamine deficiency in elderly people related to age or co-morbidity?
Wilkinson TJ, Hanger HC, George PM, Sainsbury R.
Department of Health Care of the Elderly, The Princess Margaret Hospital, Christchurch, New Zealand. tim.wilkinson@chmeds.ac.nz
OBJECTIVES: to compare erythrocyte thiamine pyrophosphate concentrations in elderly people with those in healthy younger people; to determine if any differences can be attributed to age or to co-morbidities. DESIGN: cross-sectional and 3-year longitudinal surveys. SETTING: primary care. PATIENTS: 100 volunteer blood donors and 222 elderly people from a general practice register. MEASUREMENTS: thiamine pyrophosphate concentrations using high performance liquid chromatography; physical examination, medical and medication history; grip strength, body mass index and plasma albumin. RESULTS: the mean [95% confidence interval (CI)] thiamine pyrophosphate concentration was 152 nmol/l (147-158) in the elderly group and 224 (213-235) nmol/l in the younger group (P < 0.001). Ninety-six (43.4%) of the elderly subjects had thiamine pyrophosphate concentrations below the fifth percentile of the younger subjects (140 nmol/l). Over 3 years thiamine pyrophosphate concentrations fell in the elderly cohort by 20% (95% CI: 14.5-24.5%; P < 0.01). Thiamine pyrophosphate concentrations in 39 healthy older people were no different from those in elderly people with co-morbidity but were significantly lower than those in the younger people. Elderly people with absent vibration sense in their feet had a lower thiamine pyrophosphate concentration than the rest of the group [129 (117-142)nmol/l compared with 156 (150-162)nmol/l; P < 0.01)]. Thiamine pyrophosphate concentrations were not related to prevalent diseases, common medications, body mass index, grip strength or plasma albumin. CONCLUSION: lower thiamine pyrophosphate concentrations in elderly people appear to be related more to age itself than to co-existent illnesses.
64. Fortschr Neurol Psychiatr. 2000 Mar;68(3):113-20.
[Thiamine treatment in psychiatry and neurology]
[Article in German]
Hinze-Selch D, Weber MM, Zimmermann U, Pollmacher T.
Max-Planck-Institut fur Psychiatrie, Munchen.
Every physician knows that alcohol dependence, alcohol withdrawal and Wernicke-Korsakow-syndrome require substitution with thiamine, in acute stages even parenterally. This would be trivial if there was not the widespread fear of anaphylactic, even lethal reactions to parenteral thiamine application. The present article reviews the literature published on thiamine since 1936, when the first synthetic, parenteral thiamine preparation became available, and, on this basis, tries to give practical advice and therapeutic regimens for the treatment of thiamine deficiency states. Controlled clinical studies on indications and differential thiamine therapy have not been published. From the data that are available, the following conclusions can be drawn: 1) Acute mortality of Wernicke-Korsakow-syndrome is about 20%. 2) Oral thiamine is safe. 3) The risk for an anaphylactic shock due to parenteral thiamine administration is below 1 to 100,000. 4) Not only alcohol but any condition with either increased metabolic need (pregnancy, consuming diseases) or deficient nutrition (including eating disorders) can lead to thiamine deficiency. Therefore, we suggest: 1) Oral thiamine substitution with at least 50 mg per day and supply of a sufficient and complete diet should be given to any person that might be at risk for thiamine deficiency. 2) Any patient suspicious for acute thiamine deficiency needs to be treated under inpatient conditions and there needs to receive 50 to 100 mg thiamine intravenously 3 to 4 times a day. 3) General practitioners, psychiatrists and neurologists should take care of the oral supplementation of thiamine, sufficient nutrition, and they are the physicians to diagnose early stages of thiamine deficiency.
65. Presse Med. 2000 Feb 12;29(5):240-1.
Comment in: Presse Med. 2000 Jun 24;29(22):1231.
[Right heart failure caused by thiamine deficiency (cardiac beriberi)]
[Article in French]
Akpan T, Peschard S, Brinkane AH, Bergheul S, Leroy-Terquem E, Levy R.
Service de Medecine interne, CHI Meulan, Les Mureaux.
BACKGROUND: Vitamin B1 deficiency (beriberi) is very uncommon in France. It leads to high output cardiac failure totally different from the situation observed in alcoholic patients. We report a typical case of cardiac beriberi. CASE REPORT: The patient was referred for dyspnea with high output cardiac failure. Echocardiography evidenced severe pulmonary hypertension and high cardiac output. The more common causes of heart failure were ruled out. The dietary habits of the patient (suggested beriberi which was confirmed by the low serum thiamin and therapeutic test with vitamin B1. DISCUSSION: High output cardiac failure should suggest possible Shoshin beriberi, particularly in subjects with imported dietary habits living in a precarious socioeconomic situation.
66. No To Shinkei. 2000 Jan;52(1):59-63.
[A case of Wernicke-Korsakoff syndrome with dramatic improvement in consciousness immediately after intravenous infusion of thiamine]
[Article in Japanese]
Kikuchi A, Chida K, Misu T, Okita N, Nomura H, Konno H, Takase S, Takeda A, Itoyama Y.
Department of Neurology, Kohnan Hospital, Sendai, Japan.
A 68-year-old man was hospitalized on March 4, 1998 for disturbances in consciousness. In 1995, he had received proximal subtotal gastrectomy and reconstructive surgery of the jejunal interposition for gastric cancer. Thereafter he had been taking enough food without the habit of taking liquor. In October 1997, his short term memory was becoming gradually worse. On February 12, 1998, he suffered from numbness in the feet, and then dysphagia, unsteady gait, and diplopia developed gradually. On February 26, brain MRI showed no abnormalities. On March 3, he had a fever of 38.5 degrees C and his consciousness became unclear. Neurological examination revealed semi-coma, total ophthalmoplegia, and absence of doll's eye movement. Deep tendon reflexes were absent. The serum thiamine level was 9 ng/ml (normal range: 20-50). Brain MRI demonstrated symmetrical high intensity lesions in the periaqueductal area of the midbrain, dorsomedial nuclei of bilateral thalami, and vestibular nuclei. About 30 seconds after intravenous infusion of thiamine, his consciousness improved dramatically, but returned to semi-coma after about two minutes. Wernicke-Korsakoff syndrome usually occurs acutely. In the present case, however, the disease showed slow onset, chronic progression, and then rapid worsening after fever. Reconstructive surgery of the jejunal interposition might have caused the slow onset of Wernicke-Korsakoff syndrome, and fever might have facilitated the rapid progression of the disease. An immediate high concentration of thiamine modifies the kinetics of acetylcholine receptor ion channels, thereby maintaining wakefulness, and the level of consciousness may change dramatically.
67. Hunan Yi Ke Da Xue Xue Bao. 1998;23(1):27-30.
[Thiamine status of university teacher families in Changsha]
[Article in Chinese]
Huang S, Ren G.
Department of Nutrition and Food Hygiene, Hunan Medical University, Changsha.
To evaluate the thiamine status of the population consuming the refined cereals and its products, we studied thiamine concentration in 23 food samples and human urine, and three-day dietary survey was conducted. The results showed that the thiamine content in the staple food was much lower than that in the raw material. The thiamine intake from diet was below to 80% RDA in 42.8% investigated families and the thiamine energy ratio was lower than 0.5 mg/4186.8 kJ in 71.5% of them. For the ratio of urinary tiamine (mg)/urinary inosine (g), 51.3% subjects exhibited decreased excretion, especially in the school-age children. We conclude that those people who take the refined cereals and its products as a staple food, is in the risk of thiamine deficiency.
68. Ann N Y Acad Sci. 1999;893:404-11.
Mechanisms of selective neuronal cell death due to thiamine deficiency.
Todd K, Butterworth RF.
Neuroscience Research Unit, Centre Hospitalier de l'Universite de Montreal, Quebec, Canada. kgtodd@ualberta.ca
Multiple mechanisms contribute to the selective brain lesions observed in WKS and experimental thiamine deficiency. Recent evidence of early microglial activation and increased free radical production suggest that oxidative stress processes play an important early role in the brain damage associated with thiamine deficiency.
69. Ann Vasc Surg. 2000 Jan;14(1):37-43.
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