Holo-Transcobalamin Is an Early Marker of Changes in Cobalamin Homeostasis. A Randomized Placebo-controlled Study

Abstract Background: We examined the effect of oral vitamin B12 treatment on fluctuations in plasma total cobalamin and its binding proteins transcobalamin (TC) and haptocorrin (HC). Methods: Patients (n = 88; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to daily oral treatment with (a) vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (b) vitamin B12 and folic acid; (c) vitamin B6; or (d) placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. Results: The intraindividual variation for patients not treated with B12 was ∼10% for plasma total cobalamin, total TC, apo-TC, and apo-HC, and <20% for holo-TC and TC saturation. In B12-treated patients, the maximum change in concentrations was observed already after 3 days for total TC (−16%), holo-TC (+54%), and TC saturation (+82%). At this time holo-HC (+20%) and plasma total cobalamin (+28%) showed an initial burst, but had increased further at 84 days. All changes were highly significant compared with the control group (P <0.0001). Conclusions: Oral vitamin B12 treatment produces maximal effects on total TC, holo-TC, and TC saturation within 3 days, whereas maximal increases in holo-HC and plasma total cobalamin occur later. The results support the view that holo-TC is an early marker of changes in cobalamin homeostasis.

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Plasma Vitamin B6 Vitamers before and after Oral Vitamin B6 Treatment: A Randomized Placebo-controlled Study

Clinical Chemistry ◽

10.1373/49.1.155 ◽

2003 ◽

Vol 49 (1) ◽

pp. 155-161 ◽

Cited By ~ 46

Author(s):

Mustafa Vakur Bor ◽

Helga Refsum ◽

Marianne R Bisp ◽

Øyvind Bleie ◽

Jorn Schneede ◽

...

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Vitamin B6 ◽

Oral Treatment ◽

Prolonged Treatment ◽

Controlled Study ◽

Plasma Vitamin ◽

Additional Increase ◽

Before And After ◽

B Vitamin

Abstract Background: Vitamin B6 has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B6 vitamers, pyridoxal 5′-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B6 supplementation. Methods: Patients (n = 90; age range, 38–80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B12 (0.4 mg), folic acid (0.8 mg), and vitamin B6 (40 mg); (B), vitamin B12 and folic acid; (C), vitamin B6; or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. Results: Before treatment, PLP (range, 5–111 nmol/L) and 4-PA (6–93 nmol/L) were the predominant B6 vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B6 (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were ∼10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment. Conclusions: Vitamin B6 treatment has an immediate effect on the concentrations and the forms of B6 vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B6 vitamers in plasma reflect vitamin B6 intake.

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Detectable Unmetabolized Folic Acid, and Sufficient Folate and Vitamin B12 Concentrations Are Evident in Canadian Children with Sickle Cell Disease

Current Developments in Nutrition ◽

10.1093/cdn/nzaa054_172 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1100-1100

Author(s):

Brock Williams ◽

Heather McCartney ◽

Yvonne Lamers ◽

Suzanne Vercauteren ◽

John Wu ◽

...

Keyword(s):

Folic Acid ◽

Sickle Cell Disease ◽

Vitamin B12 ◽

Sickle Cell ◽

Vitamin B6 ◽

Serum Folate ◽

High Dose ◽

Cell Disease ◽

Median Serum ◽

B Vitamin

Abstract Objectives Canadian children with sickle cell disease (SCD) are routinely supplemented with high-dose folic acid (1 mg/d), synthetic folate, due to increased erythrocyte production and turn-over in the disease. Folate also plays a vital role in one-carbon metabolism. Impairments in this folate-dependent mechanism can also occur due to secondary B-vitamin (vitamin B2, B6 and B12) deficiencies. The study objective was to determine B-vitamin status in Canadian children with SCD. Methods Serum and plasma samples from children diagnosed with SCD were obtained from BC Children's Hospital BioBank (Vancouver, Canada). Samples were analyzed for folate, vitamin B6, and related metabolites using electrospray ionization-liquid chromatography-tandem mass spectrometry. Vitamin B12 concentrations were analyzed using chemiluminescent immunoassay. World Health Organization cut-offs were used to determine deficiencies of folate (<10 nmol/L) and vitamin B12 (<150 pmol/L), and European Food Safety Authority Panel cut-offs were used for vitamin B6 (<30 nmol/L pyridoxal 5’-phosphate; PLP). Medians with interquartile ranges (IQR) are presented. Results Six individuals (50% male; SCD type: Hgb SS n = 3, Hgb SC n = 2, HbSβ,0-Thal n = 1) were included. Median age of participants was 15 (9, 18) years. Half (50%) of participants were prescribed hydroxyurea (median dose: 21(14, 30) mg/kg/d), and all participants were prescribed 1 mg/d folic acid (adherence data not available). Median serum folate was 55.4 (43.1, 71.9) nmol/L, with levels 3 to 15 times above the cut-off for deficiency. Unmetabolized folic acid (UMFA), unused folic acid in circulation, was detected in all six participants. All participants were vitamin B12 sufficient, with median plasma vitamin B12 of 325 (288, 411) nmol/L. The majority (n = 5; 83%) had sufficient B6 status, with median serum PLP of 39 (36.9, 44.2) nmol/L. Conclusions In this pilot project, there was limited evidence of B-vitamin deficiencies among Canadian children with SCD. Serum folate levels exceeded the cut-off for deficiency by 3 to 15 times, with all participants having detectable levels of UMFA. A randomized clinical trial re-assessing the routine practice of high-dose folic acid supplementation in children with SCD is warranted. Funding Sources Thrasher Research Fund and Rare Disease Foundation.

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Folic Acid, Vitamin B6, B12 Co-supplementation Effect on Inflammatory Status of Diabetic Neuropathy Patients

10.53350/pjmhs211572044 ◽

2021 ◽

Vol 15 (7) ◽

pp. 2044-2047

Author(s):

Etisa Adi Murbawani ◽

Enny Probosari ◽

Siti Fatimah Muis ◽

Heri Nugroho H.S ◽

Amalia Sukmadianti ◽

...

Keyword(s):

Folic Acid ◽

Diabetic Neuropathy ◽

Vitamin B12 ◽

Vitamin B6 ◽

Controlled Trial ◽

Vital Role ◽

Control Group ◽

Inflammatory Status ◽

Trial Subject ◽

And Control

Background: Diabetic neuropathy is common in diabetes mellitus patients with the prevalence of 50%. Inflammation takes a vital role in the complex pathogenesis of diabetic neuropathy. The decreased inflammation status is becoming a potential target of therapy and prevention of diabetes complication. Objective: to investigate the supplementation effect of vitamin B6, folic acid, and vitamin B12 in combination to inflammatory status of diabetic neuropathy patients. Method: experimental design with randomized controlled trial. Subject of study diabetic neuropathy patients. Place of study Tugurejo Hospital, Semarang in September 2018 to March 2019, with sample size of 75 subjects (treatment and control group). Results: Subjects of the study consists of 56 females and 19 males. The characteristic of subject in treatment and control group is not significantly different based on sex, vitamin B6, folic acid, vitamin B12 intake, and nutritional status. Compared with placebo, the effect of vitamin B6, folic acid, vitamin B12 co-supplementation is able to decrease serum Hs-CRP significantly with mean difference of -3.0 (CI 95% -4,95, -1,08; p <0,05. Conclusion: Co-supplementation of vitamin B6, folic acid, vitamin B12 is able to significantly decrease inflamation status. Keyword: Folic acid, vitamin B6, vitamin B12, inflammation status, diabetic neuropathy

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Faculty Opinions recommendation of Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1145088.602221 ◽

2009 ◽

Author(s):

Suzanne C Ho ◽

Roselle Lee

Keyword(s):

Folic Acid ◽

Cancer Risk ◽

Vitamin B12 ◽

Randomized Trial ◽

Vitamin B6

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Blood homocysteine, folic acid, vitamin B12 and vitamin B6 levels in psoriasis patients

TURKDERM ◽

10.4274/turkderm.22566 ◽

2017 ◽

pp. 92-97

Author(s):

Meltem Uslu ◽

Neslihan Şendur ◽

Ekin Şavk ◽

Aslıhan Karul ◽

Didem Kozacı ◽

...

Keyword(s):

Folic Acid ◽

Vitamin B12 ◽

Vitamin B6

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Relationship between Vitamin B9 (Folic Acid), Vitamin B12 (Cobalamin), and Peripheral Neuropathy in Children with Beta-Thalassemia Major

Global Medical & Health Communication (GMHC) ◽

10.29313/gmhc.v9i2.8106 ◽

2021 ◽

Vol 9 (2) ◽

Author(s):

Uni Gamayani ◽

Titin Junaidi ◽

Nushrotul Lailiyya ◽

Nur Suryawan ◽

Nanan Sekarwana

Keyword(s):

Folic Acid ◽

Peripheral Neuropathy ◽

Vitamin B12 ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Control Group ◽

Case Group ◽

Beta Thalassemia Major ◽

Vitamin B9 ◽

Significant Difference

Vitamin B9 (folic acid) and B12 (cobalamin) are essential vitamins that play roles in the process of hematopoiesis and maintaining the function of peripheral nerves. Therefore, these deficiencies may create a risk for peripheral neuropathy in beta-thalassemia major patients. The purpose of this study is to determine the relationship between vitamin B9 level, vitamin B12 level, and peripheral neuropathy in beta-thalassemia major children. It was an observational analytical study with a case-control design has been conducted at Dr. Hasan Sadikin General Hospital Bandung, Indonesia, in May–July 2019. There were 47 beta-thalassemia major children with peripheral neuropathy (case) and 41 healthy children (control). All subjects completed a general demographic questionnaire, underwent neurological examination, and were tested for vitamin B9 and B12 serum levels. Data were then analyzed using the unpaired t test to compare the vitamin levels between both groups and Spearman’s rank correlation test to investigate the correlation between vitamin levels and the number of affected nerves in the case group. Comparison of folic acid levels in the case group (21.52±6.22 ng/mL) and the control group (23.81±7.51 ng/mL) showed no significant difference (p=0.19). In contrast, cobalamin in the case group (288.57±168.61 ng/mL) and the control group (385.95±197.48 ng/mL) showed a significant difference (p=0.01). In addition, there was a moderate correlation (p=0.004, r=0.41) between folic acid level and the number of motoric nerves affected in the case group. In conclusion, cobalamin level correlates with peripheral neuropathy in beta-thalassemia major patients, and folic acid level correlates with the number of affected nerves, especially motoric nerves. HUBUNGAN ANTARA VITAMIN B9 (ASAM FOLAT), VITAMIN B12 (KOBALAMIN), DAN NEUROPATI PERIFER PADA ANAK DENGAN TALASEMIA BETA MAYORVitamin B9 (asam folat) dan B12 (kobalamin) merupakan vitamin esensial yang berperan dalam proses hematopoiesis dan menjaga fungsi saraf tepi. Defisiensi vitamin ini dapat menimbulkan risiko neuropati perifer pada pasien talasemia beta mayor. Tujuan penelitian ini mengetahui hubungan antara kadar vitamin B9, vitamin B12, dan neuropati perifer pada anak talasemia beta mayor. Metode penelitian ini adalah analitik observasional dengan rancangan studi kasus kontrol yang dilakukan di RSUP Dr. Hasan Sadikin Bandung, Indonesia pada Mei–Juli 2019. Terdapat 47 anak talasemia beta mayor dengan neuropati perifer (kelompok kasus) dan 41 anak sehat (kelompok kontrol). Seluruh subjek penelitian mengisi kuesioner demografi umum, menjalani pemeriksaan fisis neurologis, serta dilakukan tes kadar vitamin B9 dan B12 serum. Uji t test tidak berpasangan digunakan untuk membandingkan kadar vitamin pada kedua kelompok dan uji korelasi Spearman untuk membandingkan kadar kedua vitamin tersebut dengan jumlah saraf yang terkena pada kelompok kasus. Perbandingan kadar asam folat kelompok kasus (21,52±6,22 ng/mL) dan kelompok kontrol (23,81±7,51 ng/mL) menunjukkan perbedaan yang tidak bermakna (p=0,19), sedangkan perbandingan kadar kobalamin kelompok kasus (288,57±168,61 ng/mL) dan kelompok kontrol (385,95±197,48 ng/mL) menunjukkan perbedaan yang bermakna (p=0,01). Selain itu, terdapat korelasi sedang (p=0,004; r=0,41) antara kadar asam folat dam jumlah saraf motorik yang terkena pada kelompok kasus. Kesimpulan, kadar kobalamin berhubungan dengan neuropati perifer pada penderita talasemia beta mayor dan kadar asam folat berhubungan dengan jumlah saraf yang terkena, terutama saraf motorik.

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Hyperglycemia and Metformin Use Are Associated With B Vitamin Deficiency and Cognitive Dysfunction in Older Adults

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-01791 ◽

2019 ◽

Vol 104 (10) ◽

pp. 4837-4847 ◽

Cited By ~ 14

Author(s):

Kirsty M Porter ◽

Mary Ward ◽

Catherine F Hughes ◽

Maurice O’Kane ◽

Leane Hoey ◽

...

Keyword(s):

Older Adults ◽

Vitamin B12 ◽

Cognitive Dysfunction ◽

Vitamin B6 ◽

Vitamin Deficiency ◽

Community Dwelling ◽

Metformin Treatment ◽

Fortified Foods ◽

B Vitamin ◽

The Impact

AbstractContextEmerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes.ObjectiveTo determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults.Setting and ParticipantsCommunity-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment.Main Outcome MeasuresBiomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB).ResultsMetformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤−1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74).ConclusionsUse of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.

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Plasma Homocysteine, Folic Acid, and Vitamin B12 Levels in Patients With Pseudoexfoliation Syndrome, Pseudoexfoliation Glaucoma, and Normotensive Glaucoma

Medicina ◽

10.3390/medicina49050034 ◽

2013 ◽

Vol 49 (5) ◽

pp. 34 ◽

Cited By ~ 2

Author(s):

Fatih Türkcü ◽

Özlem Köz ◽

Alper Yarangümeli ◽

Veysi Öner ◽

Gülcan Kural

Keyword(s):

High Performance Liquid Chromatography ◽

Folic Acid ◽

Vitamin B12 ◽

High Performance ◽

Low Cost ◽

Plasma Homocysteine ◽

Pseudoexfoliation Syndrome ◽

Control Group ◽

Healthy Controls ◽

Pseudoexfoliation Glaucoma

Objective. The aim of this study was to evaluate the levels of plasma homocysteine (Hcy), vitamin B12, and folic acid in patients with pseudoexfoliation glaucoma (PEXG), pseudoexfoliation syndrome (PEXS), PEXS plus normotensive glaucoma (NTG).Material and Methods. In total, 24 patients with PEXG, 35 patients with PEXS, 18 patients with PEXS plus NTG, and 35 control subjects were enrolled into study. Their Hcy levels were measured by high performance liquid chromatography (HPLC); the levels of vitamin B12 and folic acid were measured by a competitive electrochemiluminescence immunoassay.Results. Higher plasma Hcy levels and lower folic acid and vitamin B12 levels were found in all 3 patients’ groups compared with the control group (all P<0.001, expect for folic acid in the PEXG group, P=0.03). Although plasma Hcy levels in the PEXG and PEXS groups were similar, the PEXS plus NTG group had significantly higher Hcy levels compared with these groups (P=0.019 and P=0.032, respectively).Conclusions. Our study showed that there was an association between hyperhomocysteinemia and PEXS either with or without glaucoma. The patients with PEXS plus NTG had higher plasma Hcy levels than the patients with PEXS or PEXG and the healthy controls. The treatment of hyperhomocysteinemia by taking low-cost vitamin B12 and folic acid preparations may prevent additional vascular problems.

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