Functional vitamin B12 deficiency in phenylketonuria patients and healthy controls: An evaluation with combined indicator of vitamin B12 status as a biochemical index

Background Vitamin B12 deficiency frequently appears in phenylketonuria patients having a diet poor in natural protein. The aims of this study were to evaluate vitamin B12 status in phenylketonuria patients by using combined indicator of vitamin B12 status (cB12) as well as methylmalonic acid and homocysteine, more specific and sensitive markers, in comparison with healthy controls. Methods Fifty-three children and adolescents with phenylketonuria under dietary treatment and 30 healthy controls were assessed cross-sectionally. Serum vitamin B12 and folate concentrations were analysed by chemiluminescence immunoassay. Plasma methylmalonic acid and total homocysteine concentrations were measured by liquid chromatography-tandem mass spectrometry and liquid chromatography, respectively. cB12 was calculated by using a formula involving blood parameters. Results Methylmalonic acid and folate concentrations in phenylketonuria group were higher compared with controls. Methylmalonic acid concentrations were high in 56.5% of the patients and 26.7% of the controls with normal vitamin B12 concentrations. Based on cB12, a significant difference within the normal values was detected between the groups. However, although 24.5% of phenylketonuria patients and 13.3% of controls had decreased vitamin B12 status according to cB12, there was no significant difference. Conclusion Children and adolescents with phenylketonuria having a strict diet can be at risk of functional vitamin B12 deficiency. This deficiency can be accurately determined by measuring methylmalonic acid concentrations. Calculation of cB12 as a biochemical index did not provide additional information compared with the measurement of methylmalonic acid alone, but may be helpful for classification of some patients with increased methylmalonic acid as having adequate vitamin B12 status.

Download Full-text

Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2008.247 ◽

2008 ◽

Vol 46 (9) ◽

Cited By ~ 18

Author(s):

Ulrich Hübner ◽

Ahmad Alwan ◽

Muhidin Jouma ◽

Mohammad Tabbaa ◽

Heike Schorr ◽

...

Keyword(s):

Vitamin B12 ◽

Methylmalonic Acid ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Serum Folate ◽

Functional Markers ◽

Unexpected Result ◽

Recurrent Abortion ◽

B12 Deficiency ◽

Low Serum

Abstract: Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid.: A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined.: Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 μmol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio.: The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion.Clin Chem Lab Med 2008;46:1265–9.

Download Full-text

The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study

10.21203/rs.3.rs-18880/v2 ◽

2020 ◽

Author(s):

Zhe-xuan Bao ◽

Xiao-wen Yang ◽

Jing Shi ◽

Yufeng Wang

Keyword(s):

Vitamin B12 ◽

Lichen Planus ◽

Serum Ferritin ◽

Oral Lichen Planus ◽

Vitamin B12 Deficiency ◽

Serum Folate ◽

Healthy Controls ◽

Significant Difference ◽

B12 Deficiency ◽

Oral Lichen

Abstract Background: Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, its causative factors and pathogenesis are not fully understood. The existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP. Methods: 236 OLP patients and 226 age-and gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed. Results: The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP. Conclusions The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.

Download Full-text

The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study

10.21203/rs.3.rs-18880/v3 ◽

2020 ◽

Author(s):

Zhe-xuan Bao ◽

Xiao-wen Yang ◽

Jing Shi ◽

Yufeng Wang

Keyword(s):

Vitamin B12 ◽

Lichen Planus ◽

Serum Ferritin ◽

Oral Lichen Planus ◽

Vitamin B12 Deficiency ◽

Serum Folate ◽

Healthy Controls ◽

Significant Difference ◽

B12 Deficiency ◽

Oral Lichen

Abstract Background: Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, and its causative factors and pathogenesis are not fully understood. Existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP.Methods: A total of 236 OLP patients and 226 age-and-gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. An REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed.Results: The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for the REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP.Conclusions: The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.

Download Full-text

The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study

10.21203/rs.3.rs-18880/v1 ◽

2020 ◽

Author(s):

Zhe-xuan Bao ◽

Xiao-wen Yang ◽

Jing Shi ◽

Yufeng Wang

Keyword(s):

Vitamin B12 ◽

Lichen Planus ◽

Serum Ferritin ◽

Oral Lichen Planus ◽

Vitamin B12 Deficiency ◽

Serum Folate ◽

Healthy Controls ◽

Significant Difference ◽

B12 Deficiency ◽

Oral Lichen

Abstract Background Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, its causative factors and pathogenesis still remain obscure. The existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP. Methods 236 OLP patients and 226 age-and gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed. Results The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP. Conclusions The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. In the case of hematinic deficiencies, appropriate supplementation therapy is necessary. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.

Download Full-text

Comparison of four automated serum vitamin B12 assays

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-0843 ◽

2015 ◽

Vol 53 (8) ◽

Cited By ~ 10

Author(s):

Emre İspir ◽

Muhittin A. Serdar ◽

Taner Ozgurtas ◽

Ozlem Gulbahar ◽

Kadir Okhan Akın ◽

...

Keyword(s):

Liquid Chromatography ◽

Vitamin B12 ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Correlation Coefficients ◽

Serum Samples ◽

Total Vitamin ◽

Significant Difference ◽

Functional Indices ◽

Roche Cobas

AbstractDiagnosis of vitamin B12 deficiency is generally based on the measurement of serum vitamin B12 levels. However, in selected cases functional indices of vitamin B12, such as methylmalonic acid (MMA) and homocysteine (HCY), are needed. Here we compare the performance of four automated total vitamin B12 assays and also investigate how these assays relate to functional indices of vitamin B12 status.Total vitamin B12, MMA and HCY were measured in 69 serum samples from routine vitamin B12 assay requests. Serum vitamin B12 analysis was performed using four different immunoassay autoanalyzers: DxI 800 Unicel (Beckman Coulter, USA), ADVIA Centaur XP (Siemens Diagnostics, Tarrytown, NY, USA), Roche Cobas E601 (Roche Diagnostics, Germany), Architect i2000sr (Abbott Laboratories, Abbott Park, IL, USA). Serum MMA levels were determined by liquid chromatography-mass spectrometry (LC-MS) and serum homocysteine levels were determined by high pressure liquid chromatography (HPLC) methods.Four immunoassay methods were comparable and correlated with each other. Correlation coefficients (r) ranged from 0.898 to 0.987, p<0.001. Highest correlation was observed between Roche Cobas – Architect i2000sr and poorest correlation was observed between DxI 800 Unicel – ADVIA Centaur comparison. DxI 800 Unicel assay demonstrated high mean bias [–122 pg/mL (–616–125 pg/mL)] and a concordance correlation coefficient (CCC) of 0.9161, lower than the others. MMA and HCY were correlated with the vitamin B12 results. The correlation coefficients with their 95% CI indicated that there was no statistically significant difference between the four methods according to their relationship with MMA and HCY.Total B12 assays correlate very well with each other. However, results of DxI 800 Unicel were lower compared to the other three autoanalyzers. All total vitamin B12 methods show similar relationships with HCY and MMA. Standardization of serum vitamin B12 assays is still not completed and further standardization studies are needed. Laboratory professionals and clinicians should be aware of this disagreement between assay methods and they should use these tests as ancillary tests.

Download Full-text

Study of vitamin B12 status and the consequential clinico-hematological profile in healthy vegetarian population in Nepal

Journal of Chitwan Medical College ◽

10.3126/jcmc.v7i1.17369 ◽

2017 ◽

Vol 7 (1) ◽

pp. 41-46

Author(s):

Pramod Paudel ◽

Jagdish Prasad Agrawal ◽

Santosh Timilsena ◽

Jyoti Subedi

Keyword(s):

Vitamin B12 ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Hemoglobin Level ◽

Cobalamin Deficiency ◽

P Value ◽

Hematological Profile ◽

Significant Difference ◽

B12 Deficiency ◽

Study Population

Background: A strict vegetarian diet has been associated with an increased risk of vitamin B12 deficiency. Clinical manifestations of cobalamin deficiency are hematologic and neurological symptoms. The purpose of this study was to determine the prevalence of vitamin B12 deficiency in healthy vegetarian population and to study the clinical and hematological profile of vitamin B12 deficient subjects.Methods: A community based cross-sectional observational study was conducted through preplanned camps in Kathmandu Nepal. 166 vegetarian people were investigated for serum vitamin B12 level and their hematological profile was done. They were examined for neurological manifestation of vitamin B12 deficiency.Results: The mean serum vitamin B12 level of the vegetarian in this study was 271.34 ±241.74 pg/ml (mean ± SD)., 53.6 % had serum vitamin B12 deficiency. 56.5 % of male and 47.1 % of female had vitamin B12 deficiency. The risk of vitamin B12 deficiency is more in males than females with odds ratio 1.201 (CI=95%) which is not statistically significant with p-value 0.312. There was no significant difference in vitamin B12 level in different age group.The study population had mean hemoglobin of 13.12 ± 1.72 gm/dl. Anemia was present in 34.9 % of study population. 33.9 % of male and 37.3 % of female had anemia. There was no significant difference in anemia in male and female vegetarian (p-value 0.72). 40% of patient who had vitamin B12 deficiency had anemia.A significant low hemoglobin level and higher MCV were found as level of serum vitamin B12 decreased. Only one patient had macrocytic anemia.There were few symptoms but not specific to vitamin B12 deficiency.Conclusion: The result of present study show that prevalence of vitamin B12 deficiency among healthy vegetarian was 53.6% with higher prevalence in male and elder age group.Prevalence of anemia was 34.9% in this study with elderly group and females being more affected.There was significant correlation between vitamin B12 and hemoglobin level and significant negative correlation with MCV. Although, not significant, leucocytes count, lymphocyte count and platelets were low in vitamin B12 deficient population.Few clinical features were present in vitamin B12 deficient subjects but neurological features specific to vitamin B12 deficiency were not seen.

Download Full-text

A Case of Subacute Combined Degeneration of Spinal Cord Diagnosed by Vitamin B12 Administration Lowering Methylmalonic Acid

Case Reports in Neurology ◽

10.1159/000505321 ◽

2020 ◽

Vol 12 (1) ◽

pp. 27-34 ◽

Cited By ~ 1

Author(s):

Daisuke Hara ◽

Masashi Akamatsu ◽

Heisuke Mizukami ◽

Bunta Kato ◽

Takaaki Suzuki ◽

...

Keyword(s):

Spinal Cord ◽

Vitamin B12 ◽

Methylmalonic Acid ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Lower Limbs ◽

Total Serum ◽

Subacute Combined Degeneration ◽

Laboratory Findings ◽

B12 Deficiency

Subacute combined degeneration of the spinal cord (SCDS) is a neurodegenerative disease characterized by subacute progression in the central and peripheral nervous systems mainly caused by vitamin B12 deficiency. It is known that typical SCDS is frequently accompanied by megaloblastic anemia and increased serum methylmalonic acid (MMA) or homocysteine (Hcy) levels on laboratory findings, and marked abnormalities on spinal cord magnetic resonance imaging (MRI). A 45-year-old woman was admitted to our hospital with a 2-year history of worsening mild weakness, numbness in bilateral lower limbs, and gait disturbance. On admission, as laboratory findings, blood count showed macrocytosis without anemia, and biochemical tests showed mild reduction in total serum vitamin B12 level and no increase of MMA and Hcy levels; there were no abnormal findings on spinal cord MRI. After administration of vitamin B12, her sensorimotor symptoms were improved and laboratory examination showed that macrocytosis was improved, serum vitamin B12 was increased, and serum MMA levels were decreased. This improved clinical course and the laboratory findings following vitamin B12 administration confirmed the diagnosis of SCDS due to vitamin B12 deficiency. SCDS presents with highly variable symptoms and laboratory findings, and observation of MMA levels and neurologic symptoms before and after vitamin B12 administration may be useful for diagnosing SCDS.

Download Full-text

The profile of hematinic deficiencies in patients with oral lichen planus: a case-control study

BMC Oral Health ◽

10.1186/s12903-020-01229-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zhe-xuan Bao ◽

Xiao-wen Yang ◽

Jing Shi ◽

Yu-feng Wang

Keyword(s):

Vitamin B12 ◽

Lichen Planus ◽

Serum Ferritin ◽

Oral Lichen Planus ◽

Vitamin B12 Deficiency ◽

Serum Folate ◽

Healthy Controls ◽

Significant Difference ◽

B12 Deficiency ◽

Oral Lichen

Abstract Background Oral lichen planus (OLP) is a relatively common mucocutaneous disorder, and its causative factors and pathogenesis are not fully understood. Existing studies on the association between hematinic deficiencies and OLP are limited and inconsistent. The aim of this study was to assess the hematinic deficiencies in a cohort of OLP patients and evaluate the correlation between hematinic deficiencies and OLP. Methods A total of 236 OLP patients and 226 age-and-gender-matched healthy controls were enrolled in this study. The levels of hemoglobin (Hb), serum folate, vitamin B12 and ferritin were measured and compared between OLP patients and healthy controls. An REU (reticular/hyperkeratotic, erosive/erythematous, ulcerative) scoring system was adopted and compared between the OLP patients with and without hematinic deficiencies. The correlation between hematinic deficiencies and OLP was analyzed. Results The frequencies of serum ferritin and vitamin B12 deficiency in OLP patients were both significantly higher than those of the healthy controls. According to gender and age, the profiles of hematinic deficiencies in OLP patients were significantly different. As for the REU score, no significant difference existed between OLP patients with and without hematinic deficiencies. Both serum ferritin deficiency and serum vitamin B12 deficiency were significantly correlated with OLP. Conclusions The present study suggested a significant association between hematinic deficiencies and OLP. Iron, folate, and vitamin B12 levels in OLP patients should be monitored routinely. Further studies are warranted to explore the interactions between OLP and hematinic deficiencies.

Download Full-text

The vitamin B12 levels in type 2 diabetes mellitus patients on metformin and not on metformin

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20210270 ◽

2021 ◽

Vol 8 (2) ◽

pp. 165

Author(s):

Ramesh Dasarathan ◽

Rajendran Velayudham ◽

Haridoss Krishnan ◽

Senthilkumar S.

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Vitamin B12 ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Metformin Therapy ◽

Significant Difference ◽

B12 Deficiency

Background: Type 2 diabetes mellitus (T2DM) is one of the major global public health concerns, metformin is one of the most widely used drugs and considered as first-line therapy for management of T2DM. Vitamin B12 malabsorption is observed in patients on metformin therapy leading to biochemical and clinical vitamin B12 deficiency. The aim of the current study was to assess the relationship between metformin therapy and development of vitamin B12 deficiency.Methods: Current observational cross sectional study was conducted at Madras medical college and Rajiv Gandhi Government general hospital. Serum vitamin B12 and other blood investigation parameters of T2DM patients, on metformin therapy for long duration (6 months or more than 2 years) were measured and correlated with vitamin B12 levels of T2DM patients not on metformin therapy. Patients were given appropriate treatment and were regularly followed up.Results: Results of the current study findings depicted that significant difference was observed in percent haemoglobin, total blood cells, platelet count, mean corpuscular volume (MCV) and albumin values of patients on metformin therapy when compared to patients who were not on metformin therapy. Study findings also revealed that substantial difference in vitamin B12 deficiency was observed in T2DM patients based on the duration of metformin therapy.Conclusions: Current study revealed that, metformin therapy for 2 years or more, can lead to significant vitamin B12 deficiency which is also associated with macrocytosis. It was concluded that longer the duration of metformin therapy, more significant would be vitamin B12 deficiency.

Download Full-text

Methylmalonic Acid and Homocysteine as Indicators of Vitamin B12 Deficiency in Patients with Gastric Cancer after Gastrectomy

Nutrients ◽

10.3390/nu11020450 ◽

2019 ◽

Vol 11 (2) ◽

pp. 450 ◽

Cited By ~ 4

Author(s):

Sae-Mi Lee ◽

Jongwon Oh ◽

Mi-Ryung Chun ◽

Soo-Youn Lee

Keyword(s):

Gastric Cancer ◽

Vitamin B12 ◽

Homocysteine Level ◽

Methylmalonic Acid ◽

Serum Vitamin ◽

Vitamin B12 Deficiency ◽

Common Complication ◽

Serum Homocysteine ◽

Median Serum ◽

B12 Deficiency

Vitamin B12 deficiency is a common complication in patients after gastrectomy. Elevated methylmalonic acid (MMA) and homocysteine are better indications of vitamin B12 deficiency than vitamin B12 serum level. We compared MMA and homocysteine levels of patients with gastric cancer after gastrectomy (n = 151) with controls (n = 142) and evaluated the prevalence of vitamin B12 deficiency using MMA and homocysteine in patients. MMA and homocysteine levels were significantly higher (p < 0.05) in patients with gastric cancer after gastrectomy. Of the 151 patients assessed after gastrectomy, 32 patients (21.2%) were vitamin B12 deficient as defined by serum MMA levels > 350 nmol/L, and 8 patients (5.3%) were vitamin B12 deficient as defined by serum homocysteine levels > 15 μmol/L. Both MMA and homocysteine levels were elevated in 7 patients. Among 33 patients with elevated MMA or homocysteine levels, 8 patients (24.2%) were vitamin B12 deficient based on a serum vitamin B12 level < 200 pg/mL. Additionally, levels of MMA and homocysteine were compared pre- and post-gastrectomy in 27 patients. The median MMA level was higher in patients with post-gastrectomy compared to pre-gastrectomy, while the median serum homocysteine level was not significantly different. These results indicate that using serum vitamin B12 levels alone may fail to detect vitamin B12 deficiency. Additional assessments of MMA and homocysteine levels are useful to evaluate possible vitamin B12 deficiency in patients who underwent a gastrectomy, and MMA is a better indicator than homocysteine to detect early changes in vitamin B12 levels.

Download Full-text