Schizophrenia-like Psychoses of Epilepsy and Disturbances of Folate and Vitamin B12Metabolism Induced by Anticonvulsant Drugs

1967 ◽  
Vol 113 (501) ◽  
pp. 911-919 ◽  
Author(s):  
E. H. Reynolds
Keyword(s):  
Psychiatric Illness ◽  
Serum Vitamin ◽  
Anticonvulsant Drug ◽  
Megaloblastic Anaemia ◽  
Vitamin B ◽  
Normal Range ◽  
Drug Induced ◽  
Subacute Combined Degeneration ◽  
Epileptic Patients ◽  
Mental Symptoms

Since it was first described by Mannheimer, Pakesch, Reimer and Vetter in 1952 megaloblastic anaemia has come to be recognized as an occasional complication of anticonvulsant drug therapy. More recently a disturbance in folic acid and vitamin B12metabolism has been observed in many non-anaemic drug-treated epileptic patients (Hawkins and Meynell, 1958; Klipstein, 1964; Malpas, Spray and Witts, 1966; Reynolds, Milner, Matthews and Chanarin, 1966a). Reynoldset al.(1966a) found megaloblastic haemopoiesis in 38 per cent. and subnormal serum folates in over 75 per cent. of a series of 54 out-patient epileptics. In addition, serum vitamin B12levels, though still within the normal range, were significantly lower in the megaloblastic group of patients than in controls. They suggested (1) that the anti-folate effects of phenobarbitone, phenytoin and primidone may be related to their therapeutic actions, and (2) that prolonged drug-induced disturbances of folate and vitamin B12metabolism may be responsible for certain side-effects, particularly mental symptoms. The latter possibility is supported by the increasing recognition of psychiatric illness due to vitamin B12deficiency in the absence of anaemia or subacute combined degeneration of the cord. (Langdon, 1905; McAlpine, 1929; Holmes, 1956; Smith, 1960; Edwin, Holten, Norum, Schrumpf and Skaug, 1965; Strachan and Henderson, 1965).

Serum B12and Folate Concentrations in Mental Patients

1967 ◽  
Vol 113 (504) ◽  
pp. 1291-1295 ◽  
Author(s):  
Richard Hunter ◽  
Muriel Jones ◽  
T. G. Jones ◽  
D. M. Matthews
Keyword(s):  
Critical Level ◽  
Serological Test ◽  
Neurological Complications ◽  
Megaloblastic Anaemia ◽  
Vitamin B ◽  
Intestinal Surgery ◽  
Clear Cut ◽  
Number Of Patients ◽  
Mental Symptoms ◽  
Wassermann Reaction

In a leading article on mental symptoms in vitamin B12deficiency (Lancet, 1965), it was pointed out that “though mental illness due to vitamin B12deficiency is uncommon, it is readily treated, and, as in general paralysis of the insane, its protean manifestations and uncertain physical signs call for an easily applied screening test comparable to the Wassermann reaction”. In the correspondence which followed it was suggested that in psychiatric practice today mental symptoms were likely to be found more frequently in association with vitamin B12deficiency than with a positive serological test for syphilis (owing in part to the increasing number of patients with deficiency syndromes following gastro-intestinal surgery); and that estimation of serum B12concentration should be performed much more readily without waiting for clear-cut haematological evidence or neurological complications of megaloblastic anaemia (Hunter and Matthews, 1965). This was emphasized by the evidence of Strachan and Henderson (1965) who described three patients with psychiatric syndromes attributed to vitamin B12deficiency in whom not only peripheral blood but also bone marrow was normal; and the report from a mental hospital in Norway by Edwin et al. (1965) that of 396 patients over the age of thirty years admitted over a twelve months period, 23 (5·8 per cent.) had serum B12concentrations below the critical level of 100 μμg. per ml. as estimated by Euglena gracilis assay. This finding was challenged by Herbert et al. (1965), who suggested that drugs of the phenothiazine group administered to the patients might have suppressed the growth of the organism, but this was disputed by Edwin et al. (1966).

scholarly journals Haematological studies on vegans

1978 ◽  
Vol 40 (1) ◽  
pp. 9-15 ◽  
Author(s):  
T. A. B. Sanders ◽  
F. R. Ellis ◽  
J. W. T. Dickerson
Keyword(s):  
Haemoglobin Concentration ◽  
Serum Vitamin ◽  
Mean Value ◽  
Serum Folate ◽  
Vitamin B ◽  
Normal Range ◽  
Blood Formation ◽  
Mean Corpuscular Haemoglobin ◽  
Erythrocyte Folate ◽  
The Mean

1. The concentrations of vitamin B12 and folate in the serum and folate in the erythrocytes were determined and full blood counts made on a series of caucasian vegans and omnivore controls.2. The blood counts and films were normal in all the vegans and no subject had a haemoglobin concentration below the lower limit of normality.3. Although within the normal range, male but not female vegans had lower values for erythrocyte counts and higher values for mean corpuscular volume and mean corpuscular haemoglobin than their controls regardless of whether they were taking vitamin B12 supplements or not.4. The mean serum vitamin B12 concentration was lower in the vegans not taking vitamin B12 supplements and in those using foods supplemented with the vitamin than in the controls, but in no subject was it below 80 ng/l.5. The serum folate concentrations were higher in the vegans than in their controls. The mean value for erythrocyte folate tended to be greater in the vegans not taking vitamin B12 supplements. No subject had an erythrocyte folate concentration of less than 100μg/l.6. It is concluded that megaloblastic anaemia is very rare in caucasian vegans and that a diet consisting entirely of plant foods is generally adequate to promote normal blood formation providing it is composed of a mixture of unrefined cereals, pulses, nuts, fruit and vegetables and is supplemented with vitamin B12.

scholarly journals Subnormal Serum Folate and Macrocytosis Associated with Anticonvulsant Drug Therapy

Blood ◽  
1964 ◽  
Vol 23 (1) ◽  
pp. 68-86 ◽  
Author(s):  
FREDERICK A. KLIPSTEIN
Keyword(s):  
Folic Acid ◽  
Drug Therapy ◽  
Acid Metabolism ◽  
Culture Media ◽  
Serum Vitamin ◽  
Anticonvulsant Drug ◽  
Serum Folate ◽  
Normal Range ◽  
Folic Acid Metabolism ◽  
Clearance Studies

Abstract Hematologic studies and microbiological assay of serum folate levels with L. casei and serum vitamin B12 concentrations with L. leichmannii were performed on 60 subjects receiving anticonvulsant drug therapy and five epileptics receiving no treatment. Subnormal serum folate levels of less than 5.0 mµg./ml. were observed in 58 per cent of 53 subjects receiving Dilantin and one of seven patients on other anticonvulsant agents. The incidence of subnormal serum folate values was greater in those subjects who had been taking Dilantin for periods of time greater than 5 years, but did not appear to bear any correlation to the dosage of the drug. Slight or moderate macrocytosis was observed in 71 per cent of subjects receiving Dilantin who had subnormal serum folate levels and in 18 per cent of subjects with normal levels. Serum B12 concentrations were within the normal range. The growth of L. casei was not inhibited by anticonvulsant drugs when added to culture media containing folic acid or serum from patients on Dilantin with normal or low folate concentrations. Folic acid clearance studies were abnormally rapid in three of nine patients studied who were receiving Dilantin. Possible sites of metabolic inhibition resulting in disturbances in folic acid metabolism during therapy with anticonvulsant medications are discussed.

scholarly journals Relation between serum vitamin B12 level and duration of treatment with carbamazepine in epilepsy patients

2016 ◽  
Vol 9 (4) ◽  
pp. 223
Author(s):  
Mohammad Tariqul Islam ◽  
Khair M. Sobhan ◽  
Mahjabin Rahman Shawly ◽  
Shafiqur Saleheen ◽  
Mohammad Masum Emran ◽  
...  
Keyword(s):  
Correlation Coefficient ◽  
Pearson Correlation ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Pearson Correlation Coefficient ◽  
Duration Of Treatment ◽  
Epileptic Patients ◽  
History Of ◽  
The Mean

<p class="Abstract">Vitamin B<sub>12</sub> levels in the serum of 58 epileptic patients receiving only carbamazepine for at least 6 months were measured. Same number of epilepsy patients with no history of taking antiepileptic medicine were taken as control. The mean level of vitamin B<sub>12</sub> in carbamazepine-treated epileptic patients was 265.5 pg/mL whereas it was 478.3 pg/mL in control. Increased duration of treatment of carbamazepine in epilepsy caused significantly decreased level of serum vitamin B<sub>12 </sub>(Pearson correlation coefficient, r = -0.9, p&lt;0.0001). In conclusion, serum vitamin B<sub>12</sub> level significantly decreased in relation to duration of carbamazepine treatment in epileptic patients.</p>

A Survey of Vitamin B12 Deficiency in an Elderly Psychiatric Population

1967 ◽  
Vol 113 (496) ◽  
pp. 241-251 ◽  
Author(s):  
R. Shulman
Keyword(s):  
Psychiatric Patients ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Pernicious Anaemia ◽  
Vitamin B ◽  
Cerebral Lesions ◽  
Mental Symptoms ◽  
B12 Deficiency ◽  
The Subject ◽  
Wassermann Reaction

For many years, cases of pernicious anaemia associated with mental symptoms have been described, and interest in these symptoms was renewed following the introduction of liver therapy (Richardson, 1929; Phillips, 1931). Interest later appeared to decline, so that MacDonald Holmes (1956), almost 20 years after the last important clinical review of the subject, could comment with justification that although the cerebral lesions of pernicious anaemia had been recognized for more than a century they were still much less familiar than the lesions which occurred in the spinal cord and peripheral nerves. Since then vitamin B12 deficiency as a cause of mental symptoms has given rise to increasing interest, and this is reflected in recent suggestions that serum vitamin B12 assays should be carried out routinely in psychiatric patients and might be more informative nowadays than the routine Wassermann reaction (Strachan and Henderson, 1965; Hunter and Matthews, 1965).

Vitamin B12Deficiency and Psychiatric Illness

1967 ◽  
Vol 113 (496) ◽  
pp. 252-256 ◽  
Author(s):  
R. Shulman
Keyword(s):  
Causal Relationship ◽  
Psychiatric Illness ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Critical Evaluation ◽  
Pernicious Anaemia ◽  
Neurological Symptoms ◽  
Vitamin B ◽  
Mental Symptoms

Many psychiatric symptoms have been described in pernicious anaemia, including depression, manic excitement, paranoid states, confusional episodes, and dementia. Although vitamin B12deficiency is known to produce neurological symptoms there is much less certainty about its role in producing mental symptoms. Despite this uncertainty, it has been asserted that carrying out vitamin B12assays on psychiatric patients will enable doctors to cure for good severe disabling disease which otherwise may end in chronicity (Edwinet al., 1966). Routine examinations to exclude pernicious anaemia have been advocated for all psychiatric patients (Strachan and Henderson, 1965; Hunter and Matthews, 1965). A prudent preliminary is a critical evaluation of the causal relationship between vitamin B12deficiency and individual psychiatric syndromes.

Vitamin B12 Deficiency Associated with Histamine2-Receptor Antagonists and a Proton-Pump Inhibitor

2002 ◽  
Vol 36 (5) ◽  
pp. 812-816 ◽  
Author(s):  
J Mark Ruscin ◽  
Robert Lee Page ◽  
Robert J Valuck
Keyword(s):  
Proton Pump Inhibitor ◽  
Gastroesophageal Reflux ◽  
Proton Pump ◽  
Serum Vitamin ◽  
Serum Folate ◽  
Dietary Vitamin ◽  
Vitamin B ◽  
Normal Range ◽  
Receptor Antagonists

OBJECTIVE: To report a case of vitamin B12 deficiency associated with long-term use (∼4½ y) of histamine2 (H2)-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 × daily in February 1990 and took various other antisecretory medications over the course of the next 4½ years. She had a normal serum vitamin B12 concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B12 concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B12–dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 μmol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B12 1000 μg/d, which confirmed vitamin B12 deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein—bound vitamin B12 from the gastrointestinal tract, suggesting that her deficiency was a result of food—cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B12 replacement. DISCUSSION: Malabsorption of dietary protein-bound vitamin B12 has been demonstrated with the use of H2-receptor antagonists and PPIs. One previous case report of vitamin B12 deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B12 is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process. CONCLUSIONS: The use of H2-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B12 and could contribute to the development of vitamin B12 deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B12 status.

scholarly journals Metabolic responses to low doses of cyanocobalamin in patients with megaloblastic anaemia

1968 ◽  
Vol 22 (4) ◽  
pp. 575-582 ◽  
Author(s):  
J. F. Adams ◽  
R. Hume ◽  
Elizabeth H. Kennedy ◽  
T. G. Pirrie ◽  
J. W. Whitelaw ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Serum Iron ◽  
Serum Vitamin ◽  
Megaloblastic Anaemia ◽  
Cobalamin Deficiency ◽  
Metabolic Responses ◽  
Vitamin B ◽  
Acid Excretion ◽  
Transient Rise ◽  
Abrupt Rise

1. The metabolic responses to daily treatment with 1 μg cyanocobalamin were studied in sixteen patients with megaloblastic anaemia due to cobalamin deficiency.2. The fall in serum iron was sluggish in most patients. The pattern of reticulocyte responses varied widely, the most common being a plateau with suboptimal maximal value.3. Urinary propionic acid excretion before treatment was normal in two out of six patients. A transient rise during treatment was observed in two patients, possibly owing to demands on coenzyme stores. The fall in urinary propionic acid excretion during treatment was slow.4. Serum vitamin B12levels rose during treatment. In two patients an abrupt rise was found, possibly owing to release of stored cobalamin into the circulation.

Serum Vitamin B12 Levels in Indian Psychiatric Patients

1970 ◽  
Vol 117 (541) ◽  
pp. 699-704 ◽  
Author(s):  
V. S. Jathar ◽  
S. P. Patrawalla ◽  
D. R. Doongaji ◽  
D. V. Rege ◽  
R. S. Satoskar
Keyword(s):  
Bone Marrow ◽  
Vitamin B12 ◽  
Peripheral Blood ◽  
Psychiatric Symptoms ◽  
Psychiatric Patients ◽  
Serum Vitamin ◽  
Pernicious Anaemia ◽  
Vitamin B ◽  
Mental Symptoms ◽  
Low Serum

It is known that pernicious anaemia is sometimes associated with mental symptoms which improve following vitamin B12 therapy (Eilenberg, 1960; Holmes, 1956; Smith, 1960). Further, it has been pointed out that such mental symptoms can occur years before the development of anaemia and no definite relationship exists between them and the severity of anaemia (Smith, 1960). Cases have been described with a variety of psychiatric symptoms and low serum vitamin B12 levels without any neurological manifestation or abnormality of peripheral blood and bone marrow. Since pernicious anaemia is due to vitamin B12 deficiency it is suspected that B12 deficiency is responsible for the mental symptoms, and serum B12 assays have been advocated routinely in psychiatric patients (Strachan and Henderson, 1965; Hunter and Matthews, 1965).

scholarly journals Haematological studies on pre-menopausal Indian and Caucasian vegetarians compared with Caucasian omnivores

1990 ◽  
Vol 64 (2) ◽  
pp. 331-338 ◽  
Author(s):  
Sheela Reddy ◽  
T. A. B. Sanders
Keyword(s):  
Vitamin C ◽  
Mean Corpuscular Volume ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Corpuscular Volume ◽  
Normal Range ◽  
Indian Women ◽  
Corpuscular Haemoglobin ◽  
Mean Corpuscular Haemoglobin ◽  
Erythrocyte Folate

Full blood counts, serum ferritin, vitamin B12 and folate, erythrocyte folate concentrations and nutrient intakes were estimated in twenty-three Indian vegetarian, twenty-two Caucasian omnivores and eighteen Caucasian vegetarian women aged 25–40 years. Energy and copper intakes were lower in the Indian women than in the Caucasians. Intakes of dietary fibre, vitamin C and folate were greater and the proportion of energy derived from fat was lower in the vegetarians than in the omnivores. Vitamin B12 and protein intakes were lower in both vegetarian groups than in the omnivores. Fe intake was similar in all the groups but haem Fe provided one-quarter of the Fe intake of the omnivores. Haemoglobin concentrations were generally inside the normal range in all groups, but were lower in the Indians as were mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH). Higher MCV, MCH and lower erythrocyte (RBC) counts were observed in Caucasian vegetarians compared with the Caucasian omnivores. In both groups of vegetarians, concentrations of serum vitamin B12 and ferritin were markedly lower than in the omnivores. RBC folate concentrations were lower in the Indians than in either of the Caucasian groups when subjects taking supplements were excluded. It is concluded that vegetarians need to ensure they have adequate intakes of Fe and vitamin B12.

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