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The Impact of Thiamine Treatment on Generalized Anxiety Disorder



Objective: Patients with generalized anxiety disorder (GAD) are fearful. They constantly worried about minor matters, and they anticipate the worst. The GAD is diagnosed when a patient experiences excessive anxiety and worry for at least 6 months. The cause of GAD is unknown. In the present paper, we discuss patients with GAD who have low levels of thiamine in their bloods. We also discuss the role of thiamine in the pathogenesis and treatment of GAD. Methods: We examined 9 patients (6 males and 3 females) who met the DSM-IV-TR diagnostic criteria for GAD. These patients had no history of alcoholism. Their ages ranged from 57 to 83 years old (mean age –72.8 ± 2.9 years). All of the patients had low blood thiamine levels (mean –25.1 nmol/L ± 6.0 nmol/L; normal level—70 nmol/L - 180 nmol/L). Participants completed the Hamilton Anxiety Rating Scale (HARS) for anxiety before and after thiamine treatments. All of the patients received daily thiamine 100 mg intramuscularly. Results: Thiamine supplementation significantly improved HARS scores, increased both appetite and general well-being, and reduced fatigue in patients with GAD. Interestingly, these patients were able to discontinue taking anxiolytic and β-blocker medications. Conclusion: Parental thiamine significantly affects patients with GAD.
International Journal of Clinical Medicine, 2011, 2, 439-443
doi:10.4236/ijcm.2011.24073 Published Online September 2011 (
Copyright © 2011 SciRes. IJCM
The Impact of Thiamine Treatment on
Generalized Anxiety Disorder
Khanh vinh quc Lương, Lan Thi Hoàng Nguyn
Vietnamese American Medical Research Foundation, Westminster, USA.
Received May 16th, 2011; revised July 15th, 2011; accepted August 20th, 2011.
Objective: Patients with generalized anxiety disorder (GAD) are fearful. They constantly worried about minor matters,
and they anticipate the worst. The GAD is diagnosed when a patient experiences excessive anxiety and worry for at
least 6 months. The cause of GAD is unknown. In the present paper, we discuss patients with GAD who have low levels
of thiamine in their bloods. We also discuss the role of thiamine in the pathogenesis and treatment of GAD. Methods:
We examined 9 patients (6 males and 3 females) who met the DSM-IV-TR diagnostic criteria for GAD. These patients
had no history of alcoholism. Their ages ranged from 57 to 83 years old (mean age –72.8 ± 2.9 years). All of the pa-
tients had low blood thiamine levels (mean –25.1 nmol/L ± 6.0 nmol/L; normal level—70 nmol/L - 180 nmol/L). Par-
ticipants completed the Hamilton Anxiety Rating Scale (HARS) for anxiety before and after thiamine treatments. All of
the patients received daily thiamine 100 mg intramuscularly. Results: Thiamine supplementation significantly improved
HARS scores, increased both appetite and general well-being, and reduced fatigue in patients with GAD. Interestingly,
these patients were able to discontinue taking anxiolytic and β-blocker medications. Conclusion: Parental thiamine
significantly affects patients with GAD.
Keywords: Thiamine, General Anxiety Disorder, Vitamin B1, Anxiety
1. Introduction
Patients with generalized anxiety disorder (GAD) are
fearful, they constantly worry about minor matters, and
they anticipate the worst. A diagnosis of GAD is made
when a patient experiences excessive anxiety and worry
for at least 6 months, involving multiple events or activi-
ties. However, the National Comorbidity Survey Repli-
cation database has indicated that many people have
GAD-like symptoms for less than 6 months. Kessler et al.
[1] suggested that the reasons for not diagnosing people
with GAD might need to be re-evaluated. An epidemiol-
ogical study reported that patients with GAD exhibit high
degrees of comorbidity with major depression (59%) and
other anxiety disorders (56%) [2]. GAD is the most dis-
abling and costly anxiety disorder seen in primary care
[3,4]. Moreover, only 18% of patients with GAD who
were followed over a 5-year period achieved full remis-
sion [5,6]. The cause of GAD is unknown. There are
many biological theories concerning the etiology of GAD,
such as the following: alterations in the structure and
function of the amygdale [7], abnormalities of the γ-
aminobutyric acid (GABA)-benzodiazepine receptor [8],
noradrenergic activation [9], serotonergic deregulation
[10], and modest genetic component [11]. Benzodiazepi-
nes are commonly used as a first-line GAD treatment.
However, newer medications such as buspirone, sero-
tonin and norepinephrine reuptake inhibitors (SNRIs)
have begun replacing benzodiazepines in the treatment of
GAD. Some patients may become dependent on benzo-
diazepines. In the meantime, the prevalence of mental
health disorders has increased in developed countries in
correlation with the Western diet [12]. Some investiga-
tors have reported that nutritional deficiencies are associ-
ated with some mental disorders [13]. Thiamine defi-
ciency, common to alcoholism, can produce confusion
and psychotic symptoms, in addition to neurological
deficits. Low plasma thiamine levels have also been ob-
served in cognitively impaired elderly patients [14].
Therefore, we examined patients with GAD who pre-
sented low levels of blood thiamine. This paper also dis-
cusses the role of thiamine in the pathogenesis and
treatment of GAD.
2. Methods and Results
We examined 9 patients (6 males and 3 females) who met
The Impact of Thiamine Treatment on Generalized Anxiety Disorder
the DSM-IV-TR diagnostic criteria for GAD. Their ages
ranged from 57 to 83 years old (mean—72.8 ± 2.9 years).
All of the patients had low blood thiamine levels (mean,
25.06 nmol/L ± 6.0 nmol/L; normal level—70 nmol/L -
180 nmol/L). These patients had no history of alcoholism;
however, they did present histories of hypertension, type
2 diabetes or both. Patients completed the Hamilton
Anxiety Rating Scale (HARS) before and one week after
thiamine treatment (the mean HARS scores were 27.33
and 5.8, respectively).The HARS has been used in nu-
merous GAD treatment studies [15]. All of the patients
received daily thiamine 100 mg intramuscularly for 2 - 4
Thiamine supplementation improved HARS scores,
increased appetite and general well-being, and decreased
fatigue in patients with GAD. Interestingly, these patients
were able to discontinue the use of anxiolytic and β-
blocker medications.
3. Discussion
In the present study, all of the patients presented low
blood thiamine levels. Thiamine is important to glucose
energy-utilization pathways, particularly in the central
nervous system, which needs a continuous supply of
glucose. Thiamine deficiency is characterized by a selec-
tive loss of neurons in the hypothalamus, midbrain,
brainstem and cerebellum of humans and animals [16,17].
Encephalopathy due to thiamine deficiency may involve
impairment of the function of cholinergic neurotransmit-
ters. Thiamine is a coenzyme that is required for the
synthesis of acetylcholine (ACh). The synthesis of ACh
is impaired in the brains of thiamine deficient rats [18],
which leads to a significant reduction of neural ACh lev-
els [19]. Using biochemical analyses, Mair et al. [20]
demonstrated that the concentration of norepinephrine
was significantly reduced in the brain of rats’ (at both the
cortex-hippocampus boundary and in the olfactory bulbs).
Furthermore, this reduction in norepinephrine was ac-
companied by a concomitant decrease in learning and
memory in the thiamine-deficient rats. Animal studies
have suggested that thiamine is involved in the presynap-
tic release of ACh. Thiamine binds to nicotinic receptors
and may exhibit anticholinesterase activity [21]. More-
over, thiamine deficiency induces an early central mus-
carinic cholinergic lesion [22]. The muscarinic choliner-
gic synaptic receptor densities were reduced by 30% in
the homogenates of the hippocampus and by 40% in the
homogenates of the temporal cortex of alcoholics [23,24].
Patients with GAD had fewer α2-adrenergic receptors
than did control subjects [25]. A blunted growth hormone
response to clonidine in patients with GAD indicated that
these patients exhibit decreased postsynaptic α2-adrener-
gic receptor sensitivity [26].
Dicethiamine hydrochloride, an analogue of thiamine,
improved performance in an animal model of complex
fatigue [27]. Sulbutiamine, a highly lipophilic thiamine
derivative, is an antiasthenic compound that can cross the
blood brain barrier and selectively active on specific
brain structures that are directly involved in asthenia [28].
Kreisler et al. [29] observed the effects of an induced
vitamin B complex deficiency that caused severe primary
mental changes or aggravations of pre-existing symp-
toms in psychotic patients. In a retrospective study,
Mishra et al. [30] investigated the relationship between
vitamin B intake in childhood and subsequent psycho-
logical distress in adulthood. They found that adult
women who consumed less thiamine during childhood
experienced more psychological distress; however, this
relationship disappeared when the authors adjusted for
smoking confound. In another study, a psychotic patient
responded to intramuscular administration of thiamine
100 mg [31]. Gontzea et al. [32] assessed the thiamine
status of patients with neurosis in a psychiatric depart-
ment. They observed decreases in thiamine excretion and
erythrocyte transketolase activity in patients with neuro-
sis compared to healthy control participants, suggesting
that the psychiatric patients had thiamine deficiencies. In
a controlled trial, Benton et al. [33] demonstrated a sig-
nificant association between improved thiamine status
and enhanced performance across a range of cognitive
function tests in women. They observed significant cog-
nitive deteriorations when the subjects were deprived of
thiamine using the psychoneurotic scales of the Minne-
sota Multiphasic Personality Inventory (MMPI); however,
thiamine supplementation reversed these effects [34].
Smidt et al. [35] found that healthy elderly Irish women
responded to thiamine supplementation with significantly
increased appetites, energy intakes, and general well-
being as well as decreased fatigue. Heseker et al. [36]
noted that low levels of thiamine, ascorbic acid and
folate associated with poor mood. Thiamine and other B
vitamins augmented tricyclicanti depressants in the
treatment of affective and cognitive disturbances in geri-
atric depression [37].Thiamine supplementation im-
proved the symptoms of neurotic patients [38]. Wilkin-
son et al. [39] noted that thiamine supplementation im-
proved the quality of life of subjects with persistently
low thiamine pyrophosphate levels. Students who took
extra thiamine had more than doubled their scores on the
clear-headedness and mood subscales of the Profile of
Mood States (POMS) psychological test [40].
The intestinal absorption of thiamine is normally suf-
ficient in young people but may decrease with age [41].
Schaller and Holler [42] reported that intestinal ALP is
involved in the active thiamine absorption in the intesti-
nal tract. Furthermore, Rindi et al. [43] found that intes-
Copyright © 2011 SciRes. IJCM
The Impact of Thiamine Treatment on Generalized Anxiety Disorder 441
tinal ALP can transphosphorylate thiamine to thiamine
monophosphate during intestinal transport in rats. With-
out ALP, thiamine cannot be transported into the lumen
of the gastrointestinal tract [44]. The decrease in intesti-
nal ALP activity that is observed in older rats has been
attributed to the reduction of enterocytes caused by the
age-induced atrophy of intestinal mucosa [45]. The en-
zymatic activity of ALP in the duodenum was also found
to be significantly higher in 5-month-old rats compared
to the other age groups; this differences stark between the
2.5-week-olds and 23-month-olds [46]. The decrease in
intestinal ALP activity of older rats has been attributed to
the reduction of the number of enterocytes caused by the
age-induced atrophy of intestinal mucosa [45].
In humans, single oral doses of thiamine above 2.5 mg
are mostly unabsorbed [47,48]. Baker et al. [49] demon-
strated that only the intramuscular administration of
thiamine was able to correct thiamine deficiencies in
subjects over 60 years-old. Sasaki et al. [50] reported a
case study of a patient with a thiamine deficiency and
psychotic symptoms. Only repeated intravenous admini-
stration thiamine ameliorated the condition of patients. In
addition, patients responded rapidly to large doses of
parental thiamine during the early stages of thiamine-
deficient encephalopathy (i.e., Wernicke’s encephalopa-
thy). The initial dose of thiamine is usually 100 mg two
to three times daily for 1 to 2 weeks.
In conclusion, parental thiamine affects the treatment
of patients with GAD patients by improving anxiety,
decreasing fatigue, and increasing appetite and general
[1] R. C. Kessler, N. Brandenburg, M. Lane, P. Roy-Byrne, P.
D. Stang, D. J. Stein and H. U. Wittchen, “Rethinking the
Duration Requirement for Generalized Anxiety Disorder:
Evidence from the National Comorbidity Survey Replica-
tion,” Psychological Medicine, Vol. 35, No. 7, 2005, pp.
1073-1082. doi:10.1017/S0033291705004538
[2] R. M. Carter, H. U. Wittchen, H. Pfister and R. C. Kessler,
“One-Year Prevalence of Subthreshold and Threshold
DSM-IV Generalized Anxiety Disorder in a Nationally
Representative Sample,” Depression and Anxiety, Vol. 13,
No. 2, 2001, pp. 78-88.
[3] M. A. Buist-Bouwman, R. De Graaf, W. A. Vollebergh, J.
Alonso, R. Bruffaerts, J. Ormel and ESEMeD/MHEDEA
2000 Investigators, “Functional Disability of Mental Dis-
orders and Comparison with Physical Disorders: A Study
among the General Population of Six European Coun-
tries,” Acta Psychiatrica Scandinavica, Vol. 113, No. 6,
2006, pp. 492-500.
[4] R. C. Kessler, P. E. Greenberg, K. D. Mickelson, L. M.
Meneades and P. S. Wang, “The Effects of Chronic
Medical Conditions on Work Loss and Work Cutback,”
Journal of Occupational and Environmental Medicine,
Vol. 43, No. 3, 2001, 218-225.
[5] C. L. Woodman, R. Noyes Jr., D. W. Black, S. Schlo-
sserand and S. J. Yagla, “A 5-Year Follow-Up Study of
Generalized Anxiety Disorder and Panic Disorder,”
Journal of Nervous & Mental Disease, Vol. 187, No. 1,
1999, pp. 3-9. doi:10.1097/00005053-199901000-00002
[6] K. A. Yonkers, M. G. Warshaw, A. O. Massion and M. B.
Keller, “Phenomenology and Course of Generalised
Anxiety Disorder,” The British Journal of Psychiatry, Vol.
168, 1996, pp. 308-313. doi:10.1192/bjp.168.3.308
[7] M. D. De Bellis, B. J. Casey, R. E. Dahl, B. Birmaher, D.
E. Williamson, K. M. Thomas, D. A. Axelson, K. Frus-
taci, A. M. Boring, J. Hall and N. D. Ryan,A Pilot
Study of Amygdala Volumes in Pediatric Generalized
Anxiety Disorder,” Biological Psychiatry, Vol. 48, No. 1,
2000, pp. 51-57. doi:10.1016/S0006-3223(00)00835-0
[8] C. Ferrarese, I. Appollonio, M. Frigo, M. Perego, R.
Piolti, M. Trabucchi and L. Frattola, “Decreased Density
of Benzodiazepine Receptors in Lymphocytes of Anxious
Patients: Reversal after Chronic Diazepam Treatment,”
Acta Psychiatrica Scandinavica, Vol. 82, No. 2, 1990, pp.
169-173. doi:10.1111/j.1600-0447.1990.tb01376.x
[9] S. Sevy, G. N. Papadimitriou, D. W. Surmont, S. Gold-
man and J. Mendlewicz, “Noradrenergic Function in Gen-
eralized Anxiety Disorder, Major Depressive Disorder,
and Healthy Subjects,” Biological Psychiatry, Vol. 25,
No. 2, 1989, pp. 141-152.
[10] M. Germine, A. W. Goddard, S. W. Woods, D. S. Char-
ney and G. R. Heninger, “Anger and Anxiety Responses
to m-Chlorophenylpiperazine in Generalized Anxiety
Disorder,” Biological Psychiatry, Vol. 32, No. 5, 1992,
pp. 457-461. doi:10.1016/0006-3223(92)90133-K
[11] K. S. Kendler, M. C. Neale, R. C. Kessler, A. C. Heath
and L. J. Eaves, “Generalized Anxiety Disorder in Women.
A Population-Based Twin Study,” Archives of General
Psychiatry, Vol. 49, No. 4, 1992, pp. 267-272.
[12] S. N. Young, “Clinical Nutrition: 3. The Fuzzy Boundary
between Nutrition and Psychopharmacology,” Canadian
Medical Association Journal, Vol. 166, No. 2, 2002, pp.
[13] R. J. Wurtman, D. O’Rourke and J. J. Wurtman, “Nutri-
ent Imbalances in Depressive Disorders. Possible Brain
Mechanisms,” Annals of the New York Academy of Sci-
ences, Vol. 575, 1989, pp. 75-82.
[14] L. Vognar and J. Stoukides, “Low Plasma Thiamin Lev-
els in Cognitively Impaired Elderly Patients Presenting
with Acute Behavioral Disturbances,”Journal of the
American Geriatrics Society, Vol. 57, No. 11, 2009, pp.
2166-2168. doi:10.1111/j.1532-5415.2009.02542.x
[15] M. Hamilton, “The Assessment of Anxiety States by Rat-
ing,” British Journal of Medical Psychology, Vol. 32, No.
1, 1959, pp. 50-55.
[16] A. Torvik, “Two Types of Brain Lesions in Wernicke’s
Copyright © 2011 SciRes. IJCM
The Impact of Thiamine Treatment on Generalized Anxiety Disorder
Encephalopathy,” Neuropathology and Applied Neurobi-
ology, Vol. 11, No. 3, 1985, pp. 179-190.
[17] K. G. Baker, A. J. Harding, G. M. Halliday, J. J. Kril and
C. G. Harper, “Neuronal Loss in Functional Zones of the
Cerebellum of Chronic Alcoholics with and without
Wernicke’s Encephalopathy,” Neuroscience, Vol. 91, No.
2, 1999, pp. 429-438.
[18] P. Ruenwongsa and S. Pattanavibag, “Impairment of Ace-
tylcholine Synthesis in Deficient Rats Developed by Pro-
longed Tea Consumption,” Life Sciences, Vol. 34, No. 4,
1984, pp. 365- 370. doi:10.1016/0024-3205(84)90625-8
[19] C. V. Vorhees, D. E. Schmidt and R. J. Barrett, “Effects
of Pyrithiamin on Acetylcholine Levels and Utilization in
Rat Brain,” Brain Research Bulletin, Vol. 3, No. 5, 1978,
pp. 493-496. doi:10.1016/0361-9230(78)90078-3
[20] R. G. Mair, C. D. Anderson, P. J. Langlais and W. J.
McEntee, “Thiamine Deficiency Depletes Cortical Nore-
pinephrine and Impairs Learning Processes in the Rat,”
Brain Research, Vol. 360, No. 1-2, 1985, pp. 273-284.
[21] K. J. Meador, M. E. Nichols, P. Franke, M. W. Durkin, R.
L. Oberzan, E. E. Moore and D. W. Loring, “Evidence for
a Central Cholinergic Effect of High-Dose Thiamine,”
Annals of Neurology, Vol. 34, No. 5, 1993, pp. 724-726.
[22] L. L. Barclay, G. E. Gibson and J. P. Blass, “Impairment
of Behavior and Acetylcholine Metabolism in Thiamine
Deficiency,” Journal of Pharmacology and Experimental
Therapeutics, Vol. 217, 1981, pp. 537-543.
[23] G. Freund and W. E. Ballinger Jr., “Loss of Muscarinic
and Benzodiazepine Neuroreceptors from Hippocampus
of Alcohol Abusers,” Alcohol, Vol. 6, No. 1, 1989, pp.
[24] G. Freund and W.E. Ballinger Jr., “Loss of Muscarinic
Cholinergic Receptors from Temporal Cortex of Alcohol
Abusers,” Metabolic Brain Disease, Vol. 4, No. 2, 1989,
pp. 121-141. doi:10.1007/BF00999390
[25] O. G. Cameron, C. B. Smith, M. A. Lee, P. J. Hollings-
worth, E. M. Hill and G. C. Curtis, “Adrenergic Status in
Anxiety Disorders: Platelet Alpha 2-Adrenergic Receptor
Binding, Blood Pressure, Pulse, and Plasma Catechola-
mines in Panic and Generalized Anxiety Disorder Patients
and in Normal Subjects,” Biological Psychiatry, Vol. 28,
No. 1, 1990, pp. 3-20.
[26] J. L. Abelson, D. Glitz, O. G. Cameron, M. A. Lee, M.
Bronzo and G. C. Curtis, “Blunted Growth Hormone Re-
sponse to Clonidine in Patients with Generalized Anxiety
Disorder,” Archives of General Psychiatry, Vol. 48, No. 2,
1991, pp. 157-162.
[27] T. Shimizu, H. Hoshino, S. Nishi, S. Nozaki and Y. Wa-
tanabe, “Anti-Fatigue Effect of Dicethiamine Hydrochlo-
ride Is Likely Associated with Excellent Absorbability
and High Transformability in Tissues as a Vitamin B1,”
European Journal of Pharmacology, Vol. 635, No. 1-3,
2010, pp. 117-123. doi:10.1016/j.ejphar.2010.02.053
[28] O. Van Reeth, “Pharmacologic and Therapeutic Features
of Sulbutiamine,” Drugs Today (Barc), Vol. 35, No. 3,
1999, pp. 187-192.
[29] O. Kreisler, E. Liebert and M. K. Horwitt, “Psychiatric
Observations on Induced Vitamin B Complex Deficiency
in Psychotic Patients,” American Journal of Psychiatry,
Vol. 105, No. 2, 1948, pp. 107-110.
[30] G. D. Mishra, S. A. McNaughton, M. A. O’Connell, C. J.
Prynne and D. Kuh, “Intake of B Vitamins in Childhood
and Adult Life in Relation to Psychological Distress
among Women in a British Birth Cohort,” Public Health
Nutrition, Vol. 12, No. 2, 2009, pp. 166-174.
[31] Y. D. Bakhai and S. Muqtadir, “Thiamine Deficiency and
Psychosis,” American Journal of Psychiatry, Vol. 144,
No. 5, 1987, pp. 687-688.
[32] I.G. Gontzea, V. Gorcea and F. Popescu, “Biochemichal
Assessment of Thiamin Status in Patients with Neurosis,”
Nutrition and Metabolism, Vol. 19, No. 3-4, 1975, pp. 53-
[33] D. Benton, J. Fordy and J. Haller, “The Impact of
Long-Term Vitamin Supplementation on Cognitive Func-
tioning,” Psychopharmacology, Vol. 117, No. 3, 1995, pp.
[34] J. Brozek and W. O. Caster, “Psychologic Effects of
Thiamine Restriction and Deprivation in Normal Young
Men,” American Journal of Clinical Nutrition, Vol. 5, No.
2, 1957, pp. 109-120.
[35] L. J. Smidt, F. M. Cremin, L. E. Grivetti and A. J. Clif-
ford, “Influence of Thiamin Supplementation on the
Health and General Well-Being of an Elderly Irish Popu-
lation with Marginal Thiamin Deficiency,” Journal of
Gerontology, Vol. 46, No. 1, 1991, pp. M16-M22.
[36] H. Heseker, W. Kuebler, J. Westenhoefer and V. Pudel,
“Psychische Veräderungen als Frühzeichen Einer Subop-
titalen Vitaminversorgung,” Ernährungsumschau, Vol. 37,
1990, pp. 87-94.
[37] I. R. Bell, J. S. Edman, F. D. Morrow, D. W. Marby, G.
Perrone, H. L. Kayne, M. Greenwald and J. O. Cole, “Vi-
tamin B1, B2, and B6 Augmentation of Tricyclic Antide-
pressant Treatment in Geriatric Depression with Cogni-
tive Dysfunction,” American Journal of Clinical Nutrition,
Vol. 11, No. 2, 1992, pp. 159-163.
[38] D. Lonsdale and R. J. Shamberger, “Red Cell Transketo-
lase as an Indicator of Nutritional Deficiency,” American
Journal of Clinical Nutrition, Vol. 33, No. 2, 1980, pp.
[39] T. J. Wilkinson, H. C. Hanger, J. Elmslie, P. M. George
and R. Sainsbury, “The Response to Treatment of Sub-
clinical Thiamine Deficiency in the Elderly,” American
Journal of Clinical Nutrition, Vol. 66, No. 4, 1997, pp.
[40] D. Benton, R. Griffiths and J. Haller, “Thiamine Supple-
mentation Mood and Cognitive Functioning,” Psycho-
pharmacology (Berl), Vol. 129, No. 1, 1997, pp. 66-71.
[41] R. A. Baum and F. L. Iber, “Thiamin-The Interaction of
Aging, Alcoholism, and Malabsorption in Various Popu-
Copyright © 2011 SciRes. IJCM
The Impact of Thiamine Treatment on Generalized Anxiety Disorder
Copyright © 2011 SciRes. IJCM
lations,” World Review of Nutrition & Dietetics, Vol. 44,
1984, pp. 85-116.
[42] K. Schaller and H. Holler, “Thiamine Absorption in Rat.
II. Intestinal Alkaline Phosphatase Activity and Thiamine
Absorption from Rat Small Intestines in-Vitro and in-
Vivo,” International Journal for Vitamin and Nutrition
Research, Vol. 45, No. 1, 1975, pp. 30-38.
[43] G. Rindi, V. Ricci, G. Gastaldi and C. Patrini, “Intestinal
Alkaline Phosphatase Can Transphosphorylate during In-
testinal Transport in the Rats,” Archives of Physiology
and Biochemistry, Vol. 103, No. 1, 1995, pp. 33-38.
[44] K. V. Q. Luong and L. T. H. Nguyen, “Adult Hypophos-
phatasia and a Low Level of Red Blood Cell Thiamine
Pyrophosphate,” Annals of Nutrition and Metabolism,
Vol. 49, No. 2, 2005, pp. 107-109.
[45] P. Höhn, H. Gabbert and R. Wagner, “Differentiation and
Aging of the Rat Intestinal Mucosa. II. Morphological,
Enzyme Histochemical and Disc Electrophoretic Aspects
of the Aging of the Small Intestinal Mucosa,” Mecha-
nisms of Ageing and Development, Vol. 7, 1978, pp. 217-
226. doi:10.1016/0047-6374(78)90068-4
[46] I. Jang, K. Jung and J. Cho, “Influence of Age on Duo-
Denal Brush Border Membrane and Specific Activities of
Brush Border Membrane Enzymes in Wistar Rats,” Ex-
perimental Animals, Vol. 49, No. 4, 2000, pp. 281-287.
[47] T. E. Friedman, T. C. Kmieckiak, P. K. Keegan and B. B.
Sheft, “The Absorption, Destruction, and Excreyion of
Orally Administered Thiamine by Human Subjects,”
Gastroenterology, Vol. 11, 1948, pp. 100-114.
[48] A. B. Morrison and J. A. Campbell, “Vitamin Absorption
Studies. I. Factors Influencing the Excretion of Oral Test
Doses of Thiamine and Riboflavin by Human Subjects,”
Journal of Nutrition, Vol. 72, 1960, pp. 435-440.
[49] H. Baker, O. Frank and S. P. Jaslow, “Oral versus Intra-
muscular Vitamin Supplement for Hypovitaminosis in the
Elderly,” Journal of the American Geriatrics Society, Vol.
28, No. 1, 1980, pp. 42-45.
[50] T. Sasaki, T. Yukizane, H. Atsuta, H. Ishikawa, T. Yo-
shiike, T. Takeuchi, K. Oshima, N. Yamamoto, A. Ku-
rumaji and T. Nishikawa, “A Case of Thiamine Defi-
ciency with Psychotic Symptoms-Blood Concentration of
Thiamine and Response to Therapy,” in Japanese, Seishin
Shinkeigaku Zasshi, Vol. 112, No. 2, 2010, pp. 97-110.
... The current work applied thiamine in a high dose of 10 mg/kg orally every other day for 30 d before exposure to chronic stress. The thiamine-treated group were able to cope signifi cantly better with stress compared to control rats as evidenced by higher BDNF and Ach content compared to controls, which suggests a role of thiamine in the enhancement of the central cholinergic system (34). However, such biochemical changes were not able to cause evident modifi cation of T maze results compared to the stress group; although thiaminetreated rats had a higher rate of alteration compared to the stress group, the difference was statistically insignificant. ...
... Thiamine is important to glucose energy-utilization pathways, particularly in the central nervous system, which needs a continuous supply of glucose. Therefore, patients whose stress symptoms include feeling sad, depressed or fatigued may benefi t from a thiamine supplement, although the mechanisms behind thiamine's stress protective activity have not been fully investigated (34,36). Moreover, thiamine pyrophosphate (TPP) is an essential cofactor required by enzymes involved in a number of important metabolic processes, including the production of acetyl-CoA and then Ach. ...
Chronic stress affects brain areas involved in learning and emotional responses through modulation of neurotropic factors or neurotransmitters. Therefore, we investigated the role of exercise and thiamine supplementation on spatial memory and on brain-derived neurotrophic factor (BDNF) and acetylcholine (Ach) content in the hippocampus of the stressed animals. Male Wistar rats were randomly assigned to 4 groups (8 rats/group): control group; stress group; swimming and stress group; and thiamine and stress group. All animals were assessed by a T maze for spatial memory or open field test for locomotion and anxiety. BDNF and Ach were estimated in the hippocampus. Chronic immobilization stress resulted in a significant decrease in BDNF and Ach levels in the hippocampus and impairment in spatial memory functions and decreased basal activity. However, either swimming training or thiamine intake for 30 d was proved to induce a significant increase both in BDNF and Ach in conjunction with improved performance in the T maze, marked anxiolytic effect and enhanced ambulation in the open field test, as compared to the stress group. Interestingly, swimming-exercised rats showed significantly higher levels of BDNF versus thiamine-receiving rats, while thiamine-receiving rats showed higher locomotor activity and less freezing behavior in the open field test compared to the swimming group. It was concluded that decreased BDNF and Ach after stress exposure could be a mechanism for the deleterious actions of stress on memory function; swimming exercise or vitamin B1 supplementation for 30 d was a protective tool to improve coping with chronic stress by modulating BDNF and Ach content along with enhancement of memory functions and motor activities.
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Thiamine or vitamin B1 is an essential, water-soluble vitamin required for mitochondrial energetics-the production of adenosine triphosphate (ATP). It is a critical and rate-limiting cofactor to multiple enzymes involved in this process, including those at the entry points and at critical junctures for the glucose, fatty acid, and amino acid pathways. It has a very short half-life, limited storage capacity, and is susceptible to degradation and depletion by a number of products that epitomize modern life, including environmental and pharmaceutical chemicals. The RDA for thiamine is 1.1-1.2 mg for adult females and males, respectively. With an average diet, even a poor one, it is not difficult to meet that daily requirement, and yet, measurable thiamine deficiency has been observed across multiple patient populations with incidence rates ranging from 20% to over 90% depending upon the study. This suggests that the RDA requirement may be insufficient to meet the demands of modern living. Inasmuch as thiamine deficiency syndromes pose great risk of chronic morbidity, and if left untreated, mortality, a more comprehensive understanding thiamine chemistry, relative to energy production, modern living, and disease, may prove useful.
The evaluation of thiamine and its derivative phosphate esters levels in pregnant women in rural communities can contribute not only for understanding the specific characteristics of this population regarding nutritional aspects, but also for clarifying the relations of psychiatric manifestations and a vitamin deficit. In the present work we assessed sociodemographic variables, psychiatric parameters and thiamine and its derivative in the whole blood of women in a rural, low-income community in Brazil. A case-control study was done. 94 women were divided in groups using the trimesters of pregnancy as a criterion: each trimester, 1st, 2nd and 3rd had 17, 37 and 38 women, respectively. A control group of non-pregnant women (n-39) was also included. Symptoms of anxiety and depression were assessed using the HAMA Scale and Beck Inventory, respectively. The thiamine and its phosphorylated derivatives concentrations were determined in whole blood samples using the HPLC method. The results suggest that physiological mechanisms linked to the metabolic pathways of thiamine may play a role in some neurobiological substrate involved in the regulation of emotional state. Thus, social vulnerability is identified as an important factor to be considered in the evaluation of the mental health of pregnant women living in rural communities.
Parkinson's disease (PD) is the second most common form of neurodegeneration in the elderly population. PD is clinically characterized by tremors, rigidity, slowness of movement and postural imbalance. A significant association has been demonstrated between PD and low levels of thiamine in the serum, which suggests that elevated thiamine levels might provide protection against PD. Genetic studies have helped identify a number of factors that link thiamine to PD pathology, including the DJ-1 gene, excitatory amino acid transporters (EAATs), the α-ketoglutarate dehydrogenase complex (KGDHC), coenzyme Q10 (CoQ10 or ubiquinone), lipoamide dehydrogenase (LAD), chromosome 7, transcription factor p53, the renin-angiotensin system (RAS), heme oxygenase-1 (HO-1), and poly(ADP-ribose) polymerase-1 gene (PARP-1). Thiamine has also been implicated in PD through its effects on L-type voltage-sensitive calcium channels (L-VSCC), matrix metalloproteinases (MMPs), prostaglandins (PGs), cyclooxygenase-2 (COX-2), reactive oxygen species (ROS), and nitric oxide synthase (NOS). Recent studies highlight a possible relationship between thiamine and PD. Genetic studies provide opportunities to determine which proteins may link thiamine to PD pathology. Thiamine can also act through a number of non-genomic mechanisms that include protein expression, oxidative stress, inflammation, and cellular metabolism. Further studies are needed to determine the benefits of using thiamine as a treatment for PD.
Several studies of representative populations have reported prevalence rates of DSM-III and DSM-III-R generalized anxiety disorder (GAD); however, no community study has examined the effect of the stricter DSM-IV criteria on prevalence estimates and patterns of comorbidity. Furthermore, past studies based on “lifetime” symptom assessments might have led to upper-bound 1-year and point prevalence estimates. Data is presented from a national representative sample study of 4,181 adults in Germany, 18–65 years old, who were interviewed for DSM-IV disorders with the 12-month version of the Munich-Composite International Diagnostic Interview. The prevalence rate of strictly defined, 12-month threshold DSM-IV GAD was estimated to be 1.5%; however, 3.6% of respondents presented with at least subthreshold syndromes of GAD during the past 12 months. Higher rates of worrying and GAD were found in women (worrying 10%, GAD 2.7%) and in older respondents (worrying 9.3%, TAD 2.2%). Taking into account a wider scope of diagnoses than previous studies, a high degree of comorbidity in GAD cases was confirmed: 59.1% of all 12-month GAD cases fulfilled criteria for major depression, and 55.9% fulfilled criteria for any other anxiety disorder. In conclusion, prevalence and comorbidity rates found for DSM-IV GAD are not substantially different from rates reported for DSM-III-R GAD. The minor differences in our findings compared to previous reports are more likely attributable to differences in study methodology rather than changes in diagnostic criteria for DSM-IV. Depression and Anxiety 13:78–88, 2001. © 2001 Wiley-Liss, Inc.
We report the case of a 63-year-old woman with thiamine deficiency who showed auditory hallucinations, a delusion of persecution, catatonic stupor, and catalepsy but no neurological symptoms including oculomotor or gait disturbance. Brain MRI did not show high-intensity T2 signals in regions including the thalami, mamillary bodies, or periaqueductal area. Her thiamine concentration was 19 ng/mL, only slightly less than the reference range of 20-50 ng/mL. Her psychosis was unresponsive to antipsychotics or electroconvulsive therapy, but was ameliorated by repetitive intravenous thiamine administrations at 100-200 mg per day. However, one month after completing intravenous treatment, her psychosis recurred, even though she was given 150 mg of thiamine per day orally and her blood concentration of thiamine was maintained at far higher than the reference range. Again, intravenous thiamine administration was necessary to ameliorate her symptoms. The present patient indicates that the possibility of thiamine deficiency should be considered in cases of psychosis without neurological disturbance and high-intensity T2 MRI lesions. Also, this case suggests that a high blood thiamine concentration does not necessarily correspond to sufficient thiamine levels in the brain. Based on this, we must reconsider the importance of a high dose of thiamine administration as a therapy for thiamine deficiency. The validity of the reference range of the thiamine concentration, 20-50 ng/mL, is critically reviewed.
The anti-fatigue effect of dicethiamine hydrochloride (DCET) was assessed and compared to that of thiamine hydrochloride (VB(1)HCl) in rats. The absorbability and tissue distribution of thiamine after oral administration of DCET and VB(1)HCl were also examined. To create fatigued animals, male SD rats were placed in plastic cages containing 1.5cm of water for 5 consecutive days. The extent of fatigue was evaluated by a weight-loaded forced swimming test. After oral administration of DCET or VB(1)HCl to non-fatigued rats, blood and tissues were serially collected to determine the concentrations of thiamine and its phosphate esters. Pharmacokinetic analysis was performed to examine the thiamine profile in the body after administration of DCET or VB(1)HCl. Swimming time was significantly shorter for the fatigued vehicle group than the non-fatigued group. DCET (30 and 100mg/kg) significantly prolonged the swimming time compared to the fatigued vehicle group. The anti-fatigue effect of VB(1)HCl (70.1mg/kg) was not significant in our set of results. Both DCET and VB(1)HCl were rapidly absorbed into the circulating blood as thiamine and eventually became localized in the organs. Thiamine was distributed at higher concentrations to the blood, heart, thigh muscles, cerebellum, hippocampus, and thalamus after administration of DCET compared to VB(1)HCl. These results indicate that DCET is a vitamin B(1) derivative that has excellent absorbability and transformability in tissues and suggest that DCET as an oral therapy may be useful against combined mental and physical fatigue, such as that often encountered in contemporary society.
Regional cerebral acetylcholine (ACh) levels and utilization rate were assessed in vivo in rats rendered thiamin deficient using the thiamin antagonists pyrithiamin or oxythiamin. ACh levels were significantly reduced in all brain regions of pyrithiamin treated rats and in the medulla-pons and striatum of oxythiamin treated rats compared to controls. ACh utilization was significantly reduced in the midbrain, striatum and hippocampus of pyrithiamin treated rats, but was reduced only in the striatum of oxythiamin treated rats compared to controls. Thus, there are some reductions in ACh levels and utilization that are unique to pyrithiamin induced deficiency and as such are distinct from oxythiamin/undernutrition related reductions. Since only pyrithiamin produces neurological symptoms, its unique ACh effects may be related to these symptoms.
At different times of day (08.00, 12.00, 16.00 and 24.00) the small intestinal mucosa of four month (adult) and 30 month (senile) old rats was examined histologically, by scanning electron microscopy, autoradiography, enzyme histochemistry and disc electrophoresis. In senile rats a villous atrophy is found histologically and an irregular architecture is found in scanning electron microscopy. The changes are essentially restricted to the proximal small intestine. The enterocytes of adult and senile rats show an identical enzyme histochemical picture. In the proximal small intestine of adult and senile rats, synchronous statistically significant fluctuations of the activity of alkaline and acid phosphatase were revealed in the disc electropherograms. Likewise statistically significant are the at all times of day low enzyme activities in the intestinal mucosa of senile rats as compared to the findings in adult rats. The fall in activity of alkaline and acid phosphatase in old rats is attributed to the numerical reduction of the enterocytes which is caused by the age atrophy of the intestinal mucosa. These findings are discussed in connection with results of our own studies of proliferation kinetics and those of other authors.
The correlations between intestinal alkaline phosphatase (IAP) activity and thiamine absorption and glucose absorption were studied in the rat. An everted sac in-vitro technique was used in adult rats whereas in-vitro experiments were performed in young rats 10 days old. All incubation experiments were done with 14-C-labeled thiamine. The patterns of IAP activity along the small intestines differed greatly between young and adult rats but were closely paralleled by the distribution of active thiamine transport in adult rats and thiamine absorption in young rats, respectively. When IAP was specifically inhibited in adult rats by L-phenylalanine active thiamine transport in-vitro was abolished. No correlation was found between IAP activity and active transport or glucose in-vitro, nor did inhibition of the enzyme in any way affect glucose transport capacity. It is suggested that the enzyme intestinal alkalinephosphatase is involved in the process of active thiamine absorption.