Article

Effect of vitamin B12 deficiency on olfactory function

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Abstract

Background: Vitamin B12 plays a major role in the maintenance of central and peripheral nervous systems. Vitamin B12 deficiency may affect the spinal cord, brain, optic nerve, and peripheral nerve functions; however, the effect of vitamin B12 deficiency on olfactory function has not been studied, so our study aimed to investigate that. Methods: Thirty-nine patients with low vitamin B12 levels and 34 controls were included in the study. All participants had detailed otorhinolaryngological examinations and laboratory tests. The Sniffin' Stick test was used for analysis of olfactory function. The 2 groups were compared for smell test results. Correlations of smell test results with demographic and laboratory data were investigated in the vitamin B12-deficient group. Results: The threshold discrimination identification scores were (mean ± standard deviation) 28.04 ± 5.58 and 35.10 ± 2.84 in the vitamin B12-deficient and control groups, respectively (p < 0.001). In the vitamin B12-deficient group, hyposmia and anosmia were evident in 56.4% and 5.1% of the patients, respectively, but no subjects in the control group had olfactory dysfunction (p < 0.001). Correlation analysis showed that age and odor identification score showed a negative correlation (p < 0.001); however, there was a positive correlation between threshold, discrimination and identification (TDI) score and vitamin B12 levels. Conclusion: In this study, we showed for the first time that olfactory dysfunction may be present in patients with vitamin B12 deficiency. Apart from a negative correlation of age with odor identification score, none of the other parameters studied showed correlations with olfactory dysfunction.

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... The etiology of anemia is multifactorial and characterized by an excessive loss of erythrocytes relative to erythrocyte production, which can occur due to nutritional deficiency, inflammation, or genetic conditions [3]. Nutritional deficiencies such as iron and vitamin B12 in anemic patients have been reported to be related with sensory disorders including hyposmia [4], olfactory craving (desiderosmia) [5], and hypogeusia [6]. In addition, anemia results in insufficient oxygen supply to various organs, which can cause behavioral dysfunction and cognitive impairment [7]. ...
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... As noted in the acupuncture section of this review, Vent et al. (2010) reported improved smell function in 2 of 15 patients following vitamin B complex treatments. More recently, in the most comprehensive study on this topic, Derin et al. (2016) tested olfaction in 39 patients with low vitamin B-12 levels and 34 controls. Tests of odor threshold, detection, and identification were 466 R.L. DOTY administered. ...
Chapter
A key concern of both the patient and physician is whether treatment is available that will eliminate or quell a given chemosensory disturbance. In cases where obvious oral, nasal, or intracranial pathology is involved, rational straightforward approaches to treatment are often available. In cases where damage to the sensory pathways is secondary to chronic inflammatory disease, trauma, viral invasion, toxic exposure, or unknown causes, the direction for therapy is more challenging. Indeed, many chemosensory disorders, if present for any period of time, cannot be reversed, while others spontaneously remit without any therapeutic intervention. This review assesses the strengths and weaknesses of more than two dozen approaches to treatment that have been suggested for a wide range of taste and smell disorders.
... It is thought that metabolites of vitamin A may play a role in regeneration of tissue in the olfactory epithelium or olfactory bulb, and this has been used intranasally to treat individuals with post-viral olfactory loss (Hummel 2017). Vitamin B12 is known to be important in the maintenance of central and peripheral nervous function, and deficiency of vitamin B12 has been associated with olfactory impairment (Derin 2016). Vitamin D deficiency has also been linked to olfactory impairment (Bigman 2020), and there is ongoing interest in the potential use of vitamin D to prevent or treat other symptoms of COVID-19 infection (Martineau 2020). ...
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Cognitive Changes and the Aging Brain - edited by Kenneth M. Heilman December 2019
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We reviewed 153 episodes of cobalamin deficiency involving the nervous system that occurred in 143 patients seen over a recent 17-year period at 2 New York City hospitals. Pernicious anemia was the most common underlying cause of the deficiency. Neurologic complaints, most commonly paresthesias or ataxia, were the first symptoms of Cbl deficiency in most episodes. The median duration of symptoms before diagnosis and treatment with vitamin B12 was 4 months, although long delays in diagnosis occurred in some patients. Diminished vibratory sensation and proprioception in the lower extremities were the most common objective findings. A wide variety of neurologic symptoms and signs were encountered, however, including ataxia, loss of cutaneous sensation, muscle weakness, diminished or hyperactive reflexes, spasticity, urinary or fecal incontinence, orthostatic hypotension, loss of vision, dementia, psychoses, and disturbances of mood. Multiple neurologic syndromes were often seen in a single patient. In 42 (27.4%) of the 153 episodes, the hematocrit was normal, and in 31 (23.0%), the mean corpuscular volume was normal. Neutropenia and thrombocytopenia were unusual even in anemic patients. In nonanemic patients in whom diagnosis was delayed, neurologic progression frequently occurred although the hematocrit remained normal. In 27 episodes, the serum cobalamin concentration was only moderately decreased (in the range of 100-200 pg/ml) and in 2 the serum level was normal. Neurologic impairment, as assessed by a quantitative severity score, was judged to be mild in 99 episodes, moderate in 39 and severe in 15. Severity of neurologic dysfunction before treatment was clearly related to the duration of symptoms prior to diagnosis. In addition, the hematocrit correlated significantly with severity, independent of the longer duration of symptoms in nonanemic patients. Four patients experienced transient neurologic exacerbations soon after beginning treatment with cyanocobalamin, with subsequent recovery. Followup evaluation was adequate to assess the neurologic response to vitamin B12 therapy in 121 episodes. All patients responded, and in 57 (47.1%), recovery was complete, with no remaining symptoms or findings on examination. The severity score was reduced by 50% or greater after treatment in 91% of the episodes. Residual long-term moderate or severe neurologic disability was noted following only 7 (6.3%) episodes. The extent of neurologic involvement after treatment was strongly related to that before therapy as well as to the duration of symptoms. The percent improvement over baseline neurologic status after treatment was inversely related to duration of symptoms and hematocrit. Some evidence of response was always seen during the first 3 months of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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"Sniffin' Sticks" is a test of nasal chemosensory function that is based on pen-like odor dispensing devices, introduced some 10 years ago by Kobal and co-workers. It consists of tests for odor threshold, discrimination, and identification. Previous work established its test-retest reliability and validity. Results of the test are presented as "TDI score", the sum of results obtained for threshold, discrimination, and identification measures. While normative data have been established they are based on a relatively small number of subjects, especially with regard to subjects older than 55 years where data from only 30 healthy subjects have been used. The present study aimed to remedy this situation. Now data are available from 3,282 subjects as compared to data from 738 subjects published previously. Disregarding sex-related differences, the TDI score at the tenth percentile was 24.9 in subjects younger than 15 years, 30.3 for ages from 16 to 35 years, 27.3 for ages from 36 to 55 years, and 19.6 for subjects older than 55 years. Because the tenth percentile has been defined to separate hyposmia from normosmia, these data can be used as a guide to estimate individual olfactory ability in relation to subject's age. Absolute hyposmia was defined as the tenth percentile score of 16-35 year old subjects. Other than previous reports the present norms are also sex-differentiated with women outperforming men in the three olfactory tests. Further, the present data suggest specific changes of individual olfactory functions in relation to age, with odor thresholds declining most dramatically compared to odor discrimination and odor identification.
Chapter
Olfaction is one of the most ancient senses. Nevertheless, the field of olfaction has received far less attention as compared to other sensory modalities. This is mostly due to the technical challenge of working with odorous stimuli and the difficulties of measuring brain activity induced by a chemosensory stimulus.
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Introduction Olfactory dysfunction has been reported to affect more than 200,000 patients a year in the USA. The aim of this survey was to obtain comparable epidemiological data and treatment information on olfactory dysfunction in German speaking countries. Methods Questionnaires were sent to all otorhinolaryngology departments in Germany, Austria and Switzerland; 52% of hospitals completed the survey. Results An average of 46 patients with olfactory dysfunction were treated per hospital every month. Hyp- and anosmia were most commonly caused by inflammatory diseases of the nose/paranasal sinuses (53%), respiratory dysfunction (19%), or postviral conditions (11%). Steroids were used most frequently for pharmacological treatment (topically 82%; orally 65%). Approximately one third of the clinics used B vitamins, or zinc; 80% of the hospitals performed surgery to treat underlying diseases. Acupuncture and smell training was used by approximately 20%. Conclusion A total of 79,000 patients per year are treated for olfactory dysfunction in German hospitals. The vast majority of these disorders (72%) is caused by sinunasal diseases. The quality control of therapeutic strategies is urgently needed.
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We report a 35-year-old patient with megaloblastic anemia who presented with features of subacute combined degeneration of the cord. Electrophysiological studies showed features of axonal neuropathy. In addition, there was evidence of prominent focal proximal conduction block in several nerves. After treatment with cyanocobalamin the neuropathy improved, and the peripheral nerve conduction block detected earlier disappeared. Reversible nerve conduction block as a feature of vitamin B12 deficiency in man, to our knowledge, has not been reported in literature, so far. © 1998 John-Wiley & Sons, Inc. Muscle Nerve 21:1341–1343, 1998.
The article deals with the case of a patient who had a partial gastrectomy and developed a vitamin B12 deficiency syndrome with anemia, myelopathy and complete loss of the senses of taste and smell. Regression of the symptoms followed liberal dosing with vitamin B12.
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'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.
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We report a patient who presented progressive cerebellar ataxia associated with vitamin B(12) deficiency. Brain magnetic resonance imaging (MRI) demonstrated a diffuse leukoencephalopathy. Six months after the initiation of methylcobalamin therapy, there were clinical improvement and reduction in the MRI abnormalities.
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Olfactory dysfunction has been reported to affect more than 200,000 patients a year in the USA. The aim of this survey was to obtain comparable epidemiological data and treatment information on olfactory dysfunction in German speaking countries. Questionnaires were sent to all otorhinolaryngology departments in Germany, Austria and Switzerland; 52% of hospitals completed the survey. An average of 46 patients with olfactory dysfunction were treated per hospital every month. Hyp- and anosmia were most commonly caused by inflammatory diseases of the nose/paranasal sinuses (53%), respiratory dysfunction (19%), or postviral conditions (11%). Steroids were used most frequently for pharmacological treatment (topically 82%; orally 65%). Approximately one third of the clinics used B vitamins, or zinc; 80% of the hospitals performed surgery to treat underlying diseases. Acupuncture and smell training was used by approximately 20%. A total of 79,000 patients per year are treated for olfactory dysfunction in German hospitals. The vast majority of these disorders (72%) is caused by sinunasal diseases. The quality control of therapeutic strategies is urgently needed.
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Multiple Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics. Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.
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Although cobalamin (vitamin B12) was isolated almost 60 years ago, its biochemical, physiologic and neurologic effects remain incompletely defined. New observations suggest renal regulation of cobalamin metabolism; actions of cobalamin on nucleic acid and protein function; and a role for cobalamin in cytokine and growth factor regulation. Clinically, no gold standard has emerged for the diagnosis of cobalamin deficiency. Moreover, cobalamin resistance may occur in diabetes, renal insufficiency and advanced age, leading to functional cobalamin deficiency despite adequate cobalamin nutriture. Finally, high-dose cobalamin therapy may have salutary pharmacologic effects on neurologic function in a variety of disorders. Many studies lacked appropriate control groups. However, at this time, therapeutic trials with pharmacologic doses of cobalamin are suggested when findings consistent with cobalamin deficiency are present regardless of the results of diagnostic tests. While oral cobalamin immediate-release is adequate for many patients, its effectiveness in reversing neurologic abnormalities has yet to be established.
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There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.
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Striking cerebral white matter abnormalities involving supratentorial regions seen on magnetic resonance imaging (MRI) scans have been described in patients with vitamin B12 deficiency. Severe involvement of infratentorial structures with partial reversibility has not been previously documented. A 54-year-old man experienced severe weight loss, associated with dementia and focal deficits. Laboratory analysis showed a severe vitamin B12 deficiency and elevated serum homocysteine. MRI scans showed a severe and diffuse white matter abnormal signal involving both the supra- and infratentorial compartments. Vitamin B12 supplementation resulted in a mild improvement in cognitive deficits and a marked resolution of imaging abnormalities. Leukoencephalopathy and dementia should raise the suspicion of a vitamin B12 deficiency because vitamin B12 supplementation may result in at least partial clinical improvement.
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Doty RL, Bromley SM, Panganiban WD. Olfactory function and dysfunction. In: Bailey BJ, Johnson JT, eds. Head and Neck Surgery–Otolaryngology. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:289–305.
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Mental and neurological disorders related to Vitamin B12 and folic acid deficiencies
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Doty RL, Jackman AH. Olfaction and gustation. In: Snow JB, Wackym PA, eds. Ballenger's Otorhinolaryngology: Head and Neck Surgery. 17th ed. Beijing: People's Medical Publishing House; 2009:465–480.
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Olfactory function and dysfunction
  • R L Doty
  • S M Bromley
  • W D Panganiban
Doty RL, Bromley SM, Panganiban WD. Olfactory function and dysfunction. In: Bailey BJ, Johnson JT, eds. Head and Neck Surgery-Otolaryngology. 4th
Ballenger's Otorhinolaryngology: Head and Neck Surgery
  • R L Doty
  • A H Jackman
Doty RL, Jackman AH. Olfaction and gustation. In: Snow JB, Wackym PA, eds. Ballenger's Otorhinolaryngology: Head and Neck Surgery. 17th ed. Beijing: People's Medical Publishing House; 2009:465-480.
Mental and neurological disorders related to Vitamin B12 and folic acid deficiencies
  • Sen