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The Impact of Thiamine Treatment on Generalized Anxiety Disorder

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Abstract

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 (http://www.SciRP.org/journal/ijcm)
Copyright © 2011 SciRes. IJCM
439
The Impact of Thiamine Treatment on
Generalized Anxiety Disorder
Khanh vinh quc Lương, Lan Thi Hoàng Nguyn
Vietnamese American Medical Research Foundation, Westminster, USA.
Email: Lng2687765@aol.com
Received May 16th, 2011; revised July 15th, 2011; accepted August 20th, 2011.
ABSTRACT
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
440
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
weeks.
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
well-being.
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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. ...
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Article
Full-text available
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.
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