Effect of vitamin B12 and folic acid deficiencies on neutrophil function.

Morphological and quantitative neutrophil abnormalities are common in the megaloblastic anemias of vitamin B12 and folic acid deficiency. Little is known, however, about the role of these vitamins in normal leukocyte function. Seven patients with megaloblastic bone marrows, four with vitamin B12 deficiency and three with folic acid deficiency, were studied to determine the effect, if any, of these deficiencies on leukocyte function. Phagocytosis of staphylococci, hexose monophosphate shunt activation with phagocytosis, and microbicidal capacity against Staphylococcus aureus were determined prior to the institution of specific therapy. In two instances, these studies were repeated following treatment. There was no impairment of phagocytosis per se, and resting metabolism was not significantly decreased. With phagocytosis, however, metabolic activation was decreased to 35%-36% of control values in the leukocytes of patients with vitamin B12 deficiency but not in the leukocytes of patients with folic acid deficiency. Bacterial killing was slightly decreased in vitamin B12 but not in folic acid deficiency. These abnormalities of function were reversed after specific therapy. These findings suggested a specific role for vitamin B12 in the production of intermediates necessary for normal cell function.     

High prevalences of vitamin B12 and folic acid deficiency in elderly subjects in Israel

The prevalences of vitamin B12 and folic acid deficiency in the general Israeli population of elders has not been assessed. We measured plasma cobalamin and folic acid concentrations in 418 subjects from four institutions for the aged, 749 subjects attending 19 geriatric day centres and 104 healthy controls. Methylmalonic acid (MMA) and/or homocysteine concentrations were determined in subjects who had a cobalamin concentration <221 pmol/l or folic acid concentration <11 nmol/l respectively. The prevalences of vitamin B12 deficiency (cobalamin <147 pmol/l and MMA > or =0.24 micromol/l), and folic acid deficiency (folic acid <11 nmol/l and homocysteine of >15 micromol/l) in subjects from day centres were 12.6% and 16.4% respectively, and in subjects from institutions 1.2% and 2.2% respectively (P < 0.001). Multiple logistic regression analysis indicated that the relative risk of living at home versus institutions for the aged was highly significant, with odds ratios (OR) of 6.8 [95% confidence interval (CI) 2.6-18.0] for vitamin B12 deficiency and 6.6 (95% CI 2.9-13.1) for folic acid deficiency. Analysis of data for day centre patients showed that folic acid deficiency was a significant risk factor of vitamin B12 deficiency (adjusted OR 3.68, 95% CI 2.27-5.98), and vitamin B12 deficiency was a significant risk of folic acid deficiency (adjusted OR 3.69, 95% CI 2.27-6.01). These data suggest that malnutrition is a major cause of the highly prevalent deficiencies of vitamin B12 and/or folic acid in elderly Israeli subjects dwelling at home.     

The effects of combined folic acid and liver extract therapy

1. Folic acid, when administered alone, did not prevent the development or progression of subacute combined degeneration in 12 of 22 patients receiving this agent for from twelve to twenty-five months.

2. One patient with total gastrectomy and a macrocytic anemia developed subacute combined degeneration after five months of folic acid therapy.

3. Neurologic disease did not develop in 6 pernicious anemia patients treated with folic acid and liver extract for three and one-half to thirty-nine months.

4. In 10 pernicious anemia patients with good nutrition, neurologic relapses did not progress when liver extract or vitamin B₁₂ therapy was instituted, even though folic acid therapy was continued. In 2 patients with abnormal nutrition and complicating organic abnormalities, nervous system disease progressed after institution of liver extract therapy.

5. Our observations are best explained by the theory that the hematologic and neurologic manifestations of pernicious anemia and other macrocytic anemias associated with gastro-intestinal tract pathology and inadequate nutrition are due to a deficiency of more than one substance. The administration of folic acid may improve the hematologic status but induce a deficiency of another substance or substances, e.g., vitamin B₁₂, which are essential for the maintenance of a normal blood picture and the integrity of the central nervous system. This deficiency will eventually result in the development of a suboptimal blood picture or subacute combined degeneration of the spinal cord, or both.

6. The hematologic status of patients with pernicious anemia is not maintained in a more satisfactory state by supplementation of liver extract or vitamin B₁₂ therapy with folic acid.

7. Folic acid therapy did not produce neurologic disease in patients with iron deficiency anemia who had free gastric hydrochloric acid in their gastric secretions and presumably sufficient intrinsic factor. It did not influence response to ferrous sulfate therapy.

8. Patients with sprue, nutritional macrocytic anemia and other macrocytic anemias associated with gastro-intestinal tract pathology who are treated with folic acid should also be given supplemental liver extract or vitamin B₁₂ to insure against the development of nervous system disease.

Submitted on April 16, 1951 Accepted on July 23, 1951     

Vitamin B 12 and folic acid serum levels in diabetics under various therapeutic regimens.

The aim of the present study was to reconsider the problem of the haematological consequences of biguanide treatment by evaluating serum vitamin B 12 and folic acid levels as well as classical haematological parameters in 30 diabetics treated by metformin. For purpose of comparison, similar evaluations were done in diabetics treated with insulin (27 patients) or sulfonylureas (13 patients). Results indicated that mean serum levels of vitamin B 12 were significantly lower in patients receiving metformin than in both other groups. In the metformin-treated group, five patients had serum levels of vitamin B 12 below 270 pg/ml and five had borderline values. No difference was found in the mean serum folic acid levels between the three groups. Similarly, there were no differences in the red blood cell counts, volumes or haemoglogin concentrations nor in the mean values of serum iron and lacticodeshydrogenase levels between the three groups. Since the haematologic and neurologic complications of vitamin B 12 deficiency may only appear after the deficiency had existed for 10-15 years, the lack of haematological alteration may be explained by the fact that the vitamin B 12 deficiency was not present for a sufficient period of time. We conclude that it may be wise to monitor the haematological values as well as vitamin B 12 levels at regular intervals in diabetic patients treated with metformin so that B 12 hypovitaminosis and its complications can be prevented.     

Functional vitamin B12 deficiency in alcoholics: An intriguing finding in a retrospective study of megaloblastic anemic patients

BackgroundMeasurement of serum cobalamin levels is the standard investigation for assessing Vitamin B12 deficiency. However some patients with clinical evidence of cobalamin deficiency may have serum levels within the normal range. Since falsely increased values of cobalamin can be caused by alcoholic liver disease, we evaluated the impact of this disease on the diagnosis of cobalamin and folic acid deficiency.MethodsWe reviewed data of 101 adult patients with megaloblastic anemia assessed by measuring in parallel serum cobalamin, serum folate and red blood cell folate levels. Further tests were performed in order to find the cause of megaloblastosis. All patients were treated with cobalamin and/or folic acid therapy.ResultsVitamin B12, folate and both deficiency were found in 86, 5 and 6 cases respectively. Normal cobalamin serum levels, normal serum and erythrocyte folate levels were found only in 3 patients, all alcohol-dependent, while in another alcoholic borderline vitamin B12 serum levels were found. All the four patients responded to cobalamin treatment.ConclusionSome alcohol-dependent patients with megaloblastic anemia may respond to vitamin B12 treatment despite normal cobalamin serum levels; therefore in alcoholics caution is urged in the interpretation of these vitamin assays, because of possible functional vitamin B12 deficiency.     

Vitamin B12 deficiency and hyperhomocysteinemia as correlates of cardiovascular risk factors in Indian subjects with coronary artery disease

Background and purposeFolate and vitamin B12 are essential components in the metabolism of homocysteine (Hcy). Hyperhomocysteinemia has been implicated in endothelial dysfunction and cardiovascular disease. However, the association of Hcy, vitamin B12, and folic acid with cardiovascular risk factors in patients with coronary artery disease (CAD) has not been studied in Indian patients. This study was conducted with the aim to evaluate the relationship of vitamin B12, folic acid, and Hcy levels with cardiovascular risk factors in subjects with known CAD.Methods and subjectsThree hundred patients (216 men; 84 women; aged 25–92 years) who had CAD on angiography were included in this study consecutively. All patients were evaluated for anthropometry and cardiovascular risk factors, and blood samples were collected for biochemical, nutritional, and inflammatory markers.ResultsPercentage of vitamin B12 and folate deficiency was 86.7% and 2.7%, respectively. Hyperhomocysteinemia was present in 95.3% patients. Vitamin B12 levels were significantly lower and Hcy levels were significantly higher in subjects with dyslipidemia, DM, and/or hypertension. Serum vitamin B12 was inversely associated with triglyceride and very low-density lipoprotein (VLDL) and positively with high-density lipoprotein (HDL). Hcy was positively associated with triglyceride and VLDL and negatively with HDL. Vitamin B12 was inversely correlated with inflammatory markers (high-sensitivity C-reactive protein and interleukin-6) directly related to insulin resistance whereas Hcy showed the opposite pattern.ConclusionsSerum vitamin B12 deficiency and hyperhomocysteinemia are related with cardiovascular risk factors in Indian patients with CAD.     

Vitamin B12 deficiency,hyperhomocysteinemia and thrombosis: a case and control study

This study aimed at assessing the relationship between thrombosis, hyperhomocysteinemia and vitamin B12 deficiency using a case–control study carried out in 326 patients with thrombosis (case group) and 351 patients from the same hospital (control group). Apart from the classic risk factors, a number of hematological variables were evaluated, including serum vitamin B12 (B12), red cell folate (RCF), and serum homocysteine (Hcy). An evaluation of serum methylmalonic acid (MMA) and a clinical study were carried out to investigate B12 pathology. Results of univariate analysis demonstrated decreased B12 levels in thrombosis (Student’s t test, p < 0.0001). Vitamin B12 below 200 pmol/l (LB200) or below 150 pmol/l (LB150), and red cell folate below 600 nmol/l were found in 17.2, 8.6, and 2.2% of cases with thromboembolism, respectively. An increase in Hcy was detected in 86 cases with thrombosis (26.3%). An abnormality in vitamin B12 and/or renal function was found in 80% of cases with hyperHcy and thrombosis. The MMA increase demonstrated that vitamin B12 deficiency was present in these patients with low levels of vitamin B12 in serum, and the MMA levels were in concordance with Hcy levels. The clinical study revealed B12 malabsorption in most cases with LB200. Multivariate analysis showed that serum vitamin B12 (RR 0.998, CI 0.997–0.999) was moderately related to thromboembolism. The results indicated that vitamin B12 deficiency was common among patients with hyperhomocysteinemia and thrombosis. Moreover, HyperHcy was caused by vitamin B12 deficiency and/or chronic renal failure in most patients with thrombosis. As the main cause of vitamin B12 deficiency was vitamin malabsorption, parenteral vitamin B12 with or without folic acid should be administered for the treatment of this condition. However, it remains to be demonstrated whether this treatment approach prevents recurrent thromboses in patients with vitamin B12 deficiency and thrombosis, as suggested by some case reports.     

Anaemia in rheumatoid arthritis: the role of iron, vitamin B12, and folic acid deficiency, and erythropoietin responsiveness.

Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13/25 (52%), vitamin B12 deficiency in 7/24 (29%), and folic acid deficiency in 5/24 (21%) of the anaemic patients. Only 8/25 (32%) had just one type of anaemia. The iron deficiency of anaemia of chronic disease (ACD) was distinguished by ferritin concentration, which was higher in that group. Mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in both anaemic groups, but most pronounced in iron deficient patients. Folic acid, and especially vitamin B12 deficiency, masked iron deficiency by increasing the MCV and MCH. Iron absorption tended to be highest in iron deficiency and lowest in ACD, suggesting that decreased iron absorption is not a cause of ACD in RA. No specific causes were found for vitamin B12 or folic acid deficiency. Haemoglobin concentration was negatively correlated with erythrocyte sedimentation rate in the group with ACD. Erythropoietin response was lower in ACD than in iron deficient patients. It was concluded that generally more than one type of anaemia is present simultaneously in anaemic patients with RA. The diagnosis of each type may be masked by another. Studies on pathogenesis of the anaemia are difficult as deficiencies generally coexist with ACD. Disease activity and, possibly, erythropoietin responsiveness are major factors in ACD pathogenesis.     

Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy.

Since gastric acid plays an important role in the absorption process of iron and vitamin B12, we determined levels of iron, ferritin, vitamin B12, and folic acid in 75 serum samples obtained during continuous omeprazole therapy (6-48 months after start of therapy) from 34 patients with peptic diseases (primarily reflux esophagitis). Serum iron and ferritin levels were decreased in two and three patients, respectively, but there is little evidence that omeprazole administration was causally related to these findings. Serum vitamin B12 and folic acid levels were normal in all cases. We conclude that iron, vitamin B12, and folic acid malabsorption is unlikely to occur, at least within the initial 3-4 years of continuous omeprazole therapy.     

Changes in serum folic acid and vitamin B12 levels in liver cirrhosis and its clinical significance]

The levels of serum folic acid and vitamin B12 were determined in 40 cases of liver cirrhosis with radioimmunoassay. It was shown that in 87.5% of the patients folic acid level was lower than that of a control group and in 67.5% serum vitamin B12 level was higher than that of the control group (P less than 0.05). The correlation between liver cirrhosis and dysbolism of folic acid and vitamin B12 and the megaloblastic changes and clinical significance were discussed.     

Subacute combined degeneration of the spinal cord; current concepts of the disease process; value of serum vitamin B12; determinations in clarifying some of the common clinical problems

Subacute combined degeneration of the spinal cord still poses many clinical problems, chiefly concerned with making an early diagnosis. The main reason for this difficulty is the lack of parallelism between the hematologic and neurologic manifestations. With the widespread administration of folic acid this problem has become more acute, since this drug may cause a hematologic remission for an indefinite period, while the neurologic signs worsen, often to an irreversible stage. Other problems concern the difficulty of distinguishing between intrinsic spinal cord disease of non-pernicious anemia type from combined system disease due to pernicious anemia; and of distinguishing pernicious anemia and subacute combined degeneration from other macrocytic anemias and their associated neurologic disturbances.

In all these difficult clinical problems the estimation of vitamin B₁₂ in the serum affords a refined diagnostic method. A low serum B₁₂ level is a reliable index of B₁₂ deficiency, and may occur with or without hematologic and/or neurologic aberrations. It is particularly useful in the diagnosis of subacute combined degeneration of the cord when the anemia is mild or absent or when the anemia has been corrected by folic acid therapy.

The practice of prescribing oral multiple vitamin preparations for patients with anemia, and more specifically of administering folic acid in the presence of vitamin B₁₂ deficiency, cannot be too strongly condemned.     

同型半胱氨酸与叶酸、维生素B12及维生素B6的关系

目的　探讨正常人群血同型半胱氨酸 (Hcy)水平分布及Hcy与年龄和性别的关系 ,Hcy水平与叶酸 ,维生素B1 2 及维生素B6之间的关系。方法　应用高效液相色谱 (HPLC)荧光检测法测定6 88例正常人血浆Hcy水平 ,用放射免疫方法测定叶酸及维生素B1 2 水平 ,用 96孔板微生物学法测定血清维生素B6水平。结果　相关分析结果显示 :血浆Hcy水平在正常人中呈非正态分布 ,随年龄增长血浆Hcy水平增加 ,男性比女性高。血浆Hcy水平与维生素B6、维生素B1 2 及叶酸水平呈负相关 (r分别为 - 0 35 4 8,- 0 2 91 6 ,- 0 32 76 ,P值均 <0 0 1 )。高Hcy血症者较非高Hcy血症者其血维生素B6、维生素B1 2 及叶酸水平均明显降低 (P值均 <0 0 1 )。结论　正常人中增高的血浆Hcy浓度与体内的维生素水平低下有关。     

Altersassoziierte Veränderungen im Vitamin-B12- und Folsäurestoffwechsel: Prävalenz, Ätiopathogenese und pathophysiologische Konsequenzen

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.     

Evidence that folic acid deficiency is a major determinant of hyperhomocysteinemia in Parkinson′s disease

In the present work we measured blood levels of total homocysteine (_tHcy), vitamin B₁₂ and folic acid in patients with Parkinson′s disease (PD) and in age-matched controls and searched for possible associations between these levels with smoking, alcohol consumption, L-DOPA treatment and disease duration in PD patients. We initially observed that plasma _tHcy levels were increased by around 30 % in patients affected by PD compared to controls. Linear correlation, multiple regression and comparative analyses revealed that the major determinant of the increased plasma concentrations of _tHcy in PD patients was folic acid deficiency, whereas in controls _tHcy levels were mainly determined by plasma vitamin B₁₂ concentrations. We also observed that alcohol consumption, gender and L-DOPA treatment did not significantly alter plasma _tHcy, folic acid and vitamin B₁₂ levels in parkinsonians. Furthermore, disease duration was positively associated with _tHcy levels and smoking was linked with a deficit of folic acid in PD patients. Considering the potential synergistic deleterious effects of Hcy increase and folate deficiency on the central nervous system, we postulate that folic acid should be supplemented to patients affected by PD in order to normalize blood Hcy and folate levels, therefore potentially avoiding these risk factors for neurologic deterioration in this disorder.     

Post-gastrectomy anemia: evaluation of 72 cases with post-gastrectomy anemia

Anemia is common in patients following gastrectomy. The purpose of this study was to document causes of anemias developing during the post-gastrectomy period and to determine the importance of complete blood count parameters on types of anemia. A total of 72 patients (23 women and 49 men) who had previously undergone gastrectomy in the past and who were admitted for the evaluation of anemia were enrolled in study. The patients who were evaluated and treated for anemia in the post-gastrectomy period were excluded. Iron deficiency anemia was present in 68 (94.4%) of 72 gastrectomized patients with anemia. Deficiencies of vitamin B12 and folate were present in 57 (79.2%) and in three patients, respectively. The most common cause of anemia was the combination of iron and vitamin B12 deficiencies. Iron deficiency was present in the majority of patients, followed by vitamin B12 deficiency in frequency. In all combinations of iron deficiency, the values of mean cell hemoglobin and mean cell hemoglobin concentration were either normal or low. In cases who had low white blood cell and platelet counts vitamin B12 deficiency was frequent, while in cases who had high numbers of white cells or platelets iron deficiency was more frequent. In conclusion, gastrectomized patients should be followed for anemia and treated appropriately based on the cause of anemia.     

The Anti-Folate Effect of Methionine on Bone Marrow of Normal and Vitamin B12 Deficient Rats

The effects of dietary vitamin B12 and methionine deficiency, and the in vitro addition of methionine, homocysteine, or folic acid on the methylation of dUMP to dTMP were studied in rat bone marrow culture. Vitamin B12 or methionine deficiency had no effect on the methylation reaction or on bone marrow folate levels although the vitamin B12 content in bone marrow was reduced in vitamin B12 deficiency. In vitro addition of vitamin B12 or folic acid also had no effect on the methylation of dUMP. In vitro addition of methionine reduced the methylation of dUMP and increased the proportion of 5-methyltetrahydrofolate at the expense of other folate coenzymes. The reason for this 'anti-folate' effect of methionine, which is the opposite to that found in liver, was not clear. The presence of 5,10-methylenetetrahydrofolate reductase and 5-methyltetrahydrofolate-homocysteine methyltransferase were confirmed in rat bone marrow and they were inhibited by S-adenosylmethionine and methionine, respectively, in a similar fashion to that found with the liver enzymes. Homocysteine had no effect on the proportions of the various folate coenzymes in bone marrow but did inhibit the incorporation of deoxyuridine and deoxythymidine into DNA. It appeared that homocysteine exerted at a non-folate dependent step beyond the formation of dTMP.     

过氧化物酶体增殖物激活受体信号通路在大鼠高脂血症发生发展中的作用

目的 探讨过氧化物酶体增殖物激活受体(PPAR) γ/Caspase-8/Caspase-3信号通路在大鼠高脂血症发生发展中的作用.方法 将健康雄性SD大鼠60只〔4周龄,体质量(110±10)g〕随机分为正常对照组、高脂饮食组、叶酸组、维生索B12组、叶酸+维生素B12组.适应性喂养1周后,叶酸组、维生索B12组、叶酸+维生素B12组分别腹腔注射叶酸(0.5 mg/d)、维生素B12 (0.05 mg/d)、叶酸(0.5mg/d)+维生素B12(0.05 mg/d),同时给予高脂饲料喂养;对照组腹腔注射0.9％NaCl溶液(0.5 ml/d)同时给予正常饲料喂养;高脂饮食组给予高脂饲料喂养.第17周末取腹主动脉利用反转录-聚合酶链反应检测各组PPARγ、Caspase-8和Caspase-3 mRNA的表达.结果 叶酸组、叶酸+维生素B12组腹主动脉的PPARγ mRNA水平高于高脂饮食组;Caspase-8、Caspase-3mRNA水平低于高脂饮食组(P＜0.05),且叶酸+维生素B12组较叶酸组降低mRNA水平更明显(P＜0.05).结论 叶酸与维生素B12可以改善血管壁PPARγ、Caspase-8和Caspase-3 mRNA的水平从而防止高脂血症对血管内皮的损伤.     

The influence of a 3-month weight reduction therapy with Orlistat on serum vitamin B12 and folic acid concentration in obese women

OBJECTIVE: Serum folic acid, but not the vitamin B(12) concentration, was found to be significantly lower in obese subjects than in the control ones. DESIGN: The aim of this study was to examine the levels of serum vitamin B(12) and folic acid in obese women before and after weight reduction therapy with Orlistat in comparison to healthy controls with normal body weight. SUBJECTS: Twenty obese women participated in a 3-month weight reduction therapy. The control group consisted of 20 healthy women. MEASUREMENTS: Body weight and height were measured and BMI was calculated. Body composition was analyzed with the impedance method using a Bodystat analyzer. In all patients before and after 3-month weight reduction therapy, serum concentrations of folic acid and vitamin B(12) were assessed. RESULTS: In obese women, serum concentrations of folic acid and vitamin B(12) did not change significantly after 3-month weight reduction therapy with Orlistat.     

A tale of two homocysteines--and two hemodialysis units

Pharmacologic doses of folic acid are commonly used to reduce the hyperhomocysteinemia of end-stage renal disease (ESRD). Vitamin B12 acts at the same metabolic locus as folic acid, but information is lacking about the specific effects of high doses of this vitamin on homocysteine levels in renal failure. We therefore compared the plasma homocysteine concentrations of maintenance hemodialysis patients in two McGill University-affiliated urban tertiary-care medical centers that differed in the use of vitamin B12 and folic acid therapy. Patients in the first hemodialysis unit are routinely prescribed high-dose folic acid (HI-F, 6 mg/d), whereas those in the second unit receive high-dose vitamin B12 in the form of a monthly 1-mg intravenous injection, along with conventional oral folic acid (HI-B12, 1 mg/d). Predialysis homocysteine was 23.4 +/- 6.8 micromol/L (mean +/- SD) in the HI-F unit and 18.2 +/- 6.1 micromol/L in the HI-B12 unit (P < .002). Postdialysis homocysteine was 14.5 +/- 4.1 in the HI-F unit and 10.6 +/- 3.4 micromol/L in the HI-B12 unit (P = .0001). Multiple regression analysis indicated that high-dose parenteral vitamin B12 was associated with a lower homocysteine concentration even after controlling for the potential confounders of sex, serum urea, serum creatinine, urea reduction ratio, and plasma cysteine. Because this was a cross-sectional observational study, we cannot exclude the possibility that unidentified factors, rather than the different vitamin therapies, account for the different homocysteine levels in the two units. Careful prospective studies of the homocysteine-lowering effect of high-dose parenteral vitamin B12 in ESRD should be undertaken.     

Prevalence of folic Acid and vitamin B12 deficiencies in patients with thyroid disorders

Although macrocytosis might occur with frequency in patients with thyroid disorders, there is controversial information on the metabolic relationship between thyroid stimulating hormone (TSH), folic acid and B12 in the general population. We performed a retrospective analysis to retrieve results of serum folic acid, B12, and TSH performed on consecutive outpatients referred by general practitioners for routine blood testing over the last 2 years. A positive, significant trend towards increased values of folic acid, but not of B12, could be observed across the spectrum of TSH values suggestive for hypo- and hyperthyroidism. However, the prevalence of subjects with folic acid or B12 deficiency did not differ significantly among the subgroups of subjects. In multivariable linear regression analysis folic acid, but not B12, was associated with TSH levels. These results do not support the routine screening for either B12 or folic acid deficiency in subjects with subclinical disturbances of thyroid function, though we can not rule out that it might still be useful in patients with overt thyroid dysfunction.