Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by blood and cerebrospinal fluid homocysteine and methylmalonic acid

2003 ◽  
Vol 9 (3) ◽  
pp. 239-245 ◽  
Author(s):  
M Vrethem ◽  
E Mattsson ◽  
H Hebelka ◽  
K Leerbeck ◽  
A Österberg ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Methylmalonic Acid ◽  
Haemoglobin Concentration ◽  
Serum Vitamin ◽  
High Serum ◽  
Plasma Homocysteine ◽  
Cobalamin Deficiency ◽  
Vitamin B ◽  
Plasma Thcy

Objective: The aim of this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. Methods: We measured serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid (C SF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in MS patients (11.6 mmol/L) compared with controls (7.4 mmol/L) (P =4-0.002). Seven patients showed low serum vitamin B12levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests of serum B12, serum MMA, mean corpuscular volume (MC V), haemoglobin concentration, C SF tHcy or C SF MMA between patients and healthy subjects. There were no correlations between C SF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum MMA, plasma tHcy, C SF Hcy or C SF MMA were not correlated to disability status, activity of disease, duration of disease or age. Conclusions:The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism relevant for the development of neuroinflammation/degeneration. O ur findings indicate that, regardless of a significant increase in plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other factors indicating vitamin B12 deficiency. A nalysis of C SF MMA and C SF tHcy, which probably reflects the brain vitamin B12 status better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.

scholarly journals Plasma homocysteine concentration is decreased by dietary intervention

2003 ◽  
Vol 89 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Marja-Leena Silaste ◽  
Maire Rantala ◽  
Georg Alfthan ◽  
Antti Aro ◽  
Y. Antero Kesäniemi
Keyword(s):  
Dietary Intervention ◽  
Serum Vitamin ◽  
Citrus Fruit ◽  
Baseline Period ◽  
Plasma Homocysteine ◽  
Serum Folate ◽  
Vitamin B ◽  
Homocysteine Concentration ◽  
Plasma Thcy ◽  
The Mean

High plasma total homocysteine (tHcy) concentration is reported to be a risk factor for vascular diseases. We investigated the extent to which serum folate and plasma tHcy respond to a high intake of natural folate from food. Thirty-seven healthy females volunteered to participate in a crossover dietary intervention. The study included a baseline period and two 5-week diet periods (low- and high-folate diets) with a 3-week washout in between. The low-folate diet contained one serving of both vegetables and frui/, while during the high-folate diet the subjects ate at least seven servings of vegetables, berries, and citrus frui/. Serum and erythrocyte (RBC) folate, serum vitamin B12, and plasma tHcy concentrations were measured at the baseline and at the end of each diet period. The mean concentrations of serum and RBC folate were 11·0 (sd 3·0) nmo/ and 412 (sd 120) nmo/ at the end of the low-folate diet and 78 (95 % CI 62, 94) % and 14 (95 % CI 8, 20) % higher in response to the high-folate diet (P<0·001). The serum concentration of vitamin B12remained unchanged during the intervention. The mean plasma tHcy concentration was 8·0 μmo/ at the end of the low-folate diet and decreased by 13 (95 % CI 9, 18) % in response to the high-folate diet (P<0·001). In conclusion, a diet high in fresh berries, citrus fruit, and vegetables effectively increases serum and RBC folate and decreases plasma homocysteine.

scholarly journals Prevalence of Vitamin B-12 Deficiency in US Adults Using the Combined Indicator of Vitamin B-12 status, cB12

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1824-1824
Author(s):  
Ekaterina Mineva ◽  
Maya Sternberg ◽  
Christine M Pfeiffer
Keyword(s):  
Mexican Americans ◽  
Methylmalonic Acid ◽  
Age Groups ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Us Congress ◽  
Funding Sources ◽  
Plasma Thcy ◽  
Younger Age ◽  
Vitamin B 12

Abstract Objectives High blood methylmalonic acid (MMA) and homocysteine (tHcy) and low serum B-12 and holotranscobalamin (holoTC) concentrations indicate vitamin B-12 deficiency. The diagnosis is often contradictory when using any test independently. A mathematical model including all 4 biomarkers, named combined indicator of vitamin B-12 status (cB12), has been proposed. Our goal was to describe cB12 in US adults and estimate the prevalence of low or transitional vitamin B-12 status compared to conventional single biomarkers. Methods We assessed cB12 in persons ≥20 y participating in NHANES from 1999 to 2004 from 3 biomarkers: serum vitamin B-12, MMA, and plasma tHcy. Results The following groups had significantly lower cB12: persons ≥70 y compared with younger age groups, males compared with females, non-Hispanic whites compared with non-Hispanic blacks and Mexican Americans, and non-users of vitamin B-12 containing supplements compared with users. Shorter fasting times and impaired renal function also resulted in lower cB12. There was a strong significant association of cB12 with serum vitamin B-12 (Spearman r = 0.75), MMA (r = −0.70), and tHcy concentrations (r = −0.59). The prevalence of vitamin B-12 deficiency varied with the biomarker and cutoff used: 2.2% and 13% for serum vitamin B-12 &lt; 148 and 148 − 222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff between 250 and 320 nmol/L; and 8.4% for tHcy &gt; 13 μmol/L. Using the proposed cB12 cutoff of &lt; −0.5, 2.7% of adults had “low or transitional vitamin B-12 status”. Conclusions Based on the new combined indicator using 3 biomarkers a larger portion of US adults had adequate vitamin B-12 status (97%) compared to conventional single biomarkers (between 85% and 94%), likely indicating the higher specificity of cB12. It is unclear whether the availability of holoTC data would change these findings. Funding Sources This work was supported by direct appropriations from US Congress.

Serum Vitamin B12 Concentrations among Mothers and Newborns and Follow-up Study to Assess Implication on the Growth Velocity and the Urinary Methylmalonic Acid Excretion

2009 ◽  
Vol 79 (56) ◽  
pp. 297-307 ◽  
Author(s):  
Laila Hussein ◽  
Sahar Abdel Aziz ◽  
Salwa Tapouzada ◽  
Boehles
Keyword(s):  
Early Diagnosis ◽  
Growth Velocity ◽  
Methylmalonic Acid ◽  
Post Partum ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Postnatal Life ◽  
Negative Consequences ◽  
Metabolic Marker ◽  
Biochemical Measurement

Objective:Cobalamin (B12) deficiency has been reported in infants born to mothers with low cobalamin intake. Early diagnosis of vitamin B12 deficiency in infants is critical for the prevention of neurobehavioral disorders. We investigated the relationship between serum vitamin B12 level in newborns and in their healthy mothers who consumed an omnivorous diet. Anthropometry was studied longitudinally to assess the growth velocity of the infants. Urinary methylmalonic acid (MMA) excretion of 6-month old infants was compared retrospectively as the biomarker correlated with the initial serum vitamin B12 concentrations. Methods: Serum cobalamin and blood hemoglobin were determined in 84 pairs of newborns and their mothers. Urinary MMA excretion was measured in the same subjects during the first 6 months of the post partum period. Results: At birth, median serum cobalamin levels were 152.0 pmol/L in the mothers and 296.6 pmol/L in the newborns. Maternal and neonatal serum cobalamin levels had no effect on growth velocity during the first six months of postnatal life. Serum maternal and neonatal cobalamin levels were inversely associated with urinary MMA excretion. Conclusion: Early diagnosis of vitamin B12 status in neonates and infants is crucial, particularly in nutritionally deprived areas. Biochemical measurement of plasma cobalamin or its metabolic marker MMA is highly recommended. Urinary MMA measurement in cobalamin diagnostics provides an advantage in that blood sampling is not required. A vitamin B12 taskforce should be created to alleviate vitamin deficiency and its negative consequences.

Effects of Mixed Dietary Supplements on Total Plasma Homocysteine Concentrations (tHcy): A Randomized, Double-Blind, Placebo-Controlled Trial

2012 ◽  
Vol 82 (4) ◽  
pp. 260-266 ◽  
Author(s):  
Salah E. Gariballa ◽  
Sarah J. Forster ◽  
Hilary J. Powers
Keyword(s):  
Older Patients ◽  
Controlled Trial ◽  
Plasma Homocysteine ◽  
Acute Illness ◽  
Vitamin B ◽  
Total Plasma ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Nutrient Supplement ◽  
Plasma Thcy

Background: Although a number of studies have reported raised total plasma homocysteine (tHcy) concentrations in free-living older people, there are no data on homocysteine response to a mixed nutrient supplement in older patients. A raised plasma homocysteine concentration in older patients is partly a reflection of their co-morbidity, including impaired renal function, and there is uncertainty about the extent to which dietary interventions can improve plasma tHcy. Aim: To determine the plasma tHcy response to dietary supplements during acute illness. Methods: Two-hundred and thirty-six hospitalized, acutely ill older patients, who were part of a randomized double-blind placebo-controlled trial, were assigned to receive a daily oral nutritional supplement drink containing 1.3 mg of vitamin B2, 1.4 mg of vitamin B6, 1.5 μg of B12, 200 μg of folic acid, or a placebo, for 6 weeks. Outcome measures were plasma tHcy concentration at baseline, 6 weeks, and 6 months. Results: The mean plasma tHcy concentration fell among patients given the supplements (mean difference 4.1 µmol/L [95 % C.I, 0.14 to 8.03), p = 0.043], but tHcy concentration increased between 6 weeks and 6 months, after patients stopped taking the supplements [mean difference -2.0 µmol/L (95 % C.I, -03.9 to -0.18), p = 0.033]. About 46 % of patients in the placebo group and 55 % of patients in the supplement group had hyperhomocysteinemia (>14 µmol/L) at baseline compared with 45 % and 29 % at the end of the treatment period. Conclusions: A mixed nutrient supplement containing physiological amounts of B vitamins significantly reduced plasma tHcy concentrations in older patients recovering from acute illness.

scholarly journals Vitamin B12 status, cognitive decline and dementia: a systematic review of prospective cohort studies

2012 ◽  
Vol 108 (11) ◽  
pp. 1948-1961 ◽  
Author(s):  
Fiona O'Leary ◽  
Margaret Allman-Farinelli ◽  
Samir Samman
Keyword(s):  
Systematic Review ◽  
Cohort Studies ◽  
Cognitive Decline ◽  
Quality Assessment ◽  
Prospective Cohort ◽  
Methylmalonic Acid ◽  
Serum Vitamin ◽  
Assessment Tools ◽  
Vitamin B ◽  
Prospective Cohort Studies

Poor vitamin B12 status may lead to the development of cognitive decline and dementia but there is a large variation in the quality, design of and results reported from these investigations. We have undertaken a systematic review of the evidence for the association between vitamin B12 status and cognitive decline in older adults. A database search of the literature to 2011 was undertaken, using keywords related to vitamin B12 and cognition. All prospective cohort studies assessing the association of serum vitamin B12 or biomarkers were included. Quality assessment and extraction of the data were undertaken by two researchers. The quality assessment tool assigns a positive, neutral or negative rating. Of 3772 published articles, thirty-five cohort studies (n 14 325 subjects) were identified and evaluated. No association between serum vitamin B12 concentrations and cognitive decline or dementia was found. However, four studies that used newer biomarkers of vitamin B12 status (methylmalonic acid and holotranscobalamin (holoTC)) showed associations between poor vitamin B12 status and the increased risk of cognitive decline or dementia diagnosis. In general, the studies were of reasonable quality (twenty-one positive, ten neutral and four negative quality) but of short duration and inadequate subject numbers to determine whether an effect exists. Future studies should be of adequate duration (at least 6 years), recruit subjects from the seventh decade, choose markers of vitamin B12 status with adequate specificity such as holoTC and/or methylmalonic acid and employ standardised neurocognitive assessment tools and not screening tests in order to ascertain any relationship between vitamin B12 status and cognitive decline.

scholarly journals Primary progressive multiple sclerosis to be treated with ocrelizumab: a mistaken case of cobalamin deficiency

2019 ◽  
Vol 12 (5) ◽  
pp. e229080 ◽  
Author(s):  
Sydney Feldman ◽  
Salman Aljarallah ◽  
Shiv Saidha
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Disorders ◽  
Progressive Multiple Sclerosis ◽  
Cobalamin Deficiency ◽  
Vitamin B ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Anti Cd20 ◽  
Mri Changes ◽  
Spine Mri

Cobalamin (vitamin B12) deficiency often manifests with neurologic symptoms and may rarely mimic multiple sclerosis (MS) among other neurological disorders. However, MRI changes associated with cobalamin deficiency are typically spinal predominant and distinct from MS-related changes. We report a case of a patient with cobalamin deficiency who was recommended by her primary neurologist to commence treatment with ocrelizumab, a potent anti-CD20 B-cell depleting monoclonal antibody, after being diagnosed with primary progressive MS. However, cervical spine MRI demonstrated changes classical of cobalamin deficiency including ‘inverted V sign’ signal hyperintensity and following parenteral cobalamin supplementation her neurological symptoms quickly and dramatically improved.

scholarly journals The experimental production of vitamin B12 deficiency in the baboon (Papio cynocephalus). A 2-year study

1974 ◽  
Vol 32 (2) ◽  
pp. 219-228 ◽  
Author(s):  
R. C Siddons
Keyword(s):  
Methylmalonic Acid ◽  
Daily Intake ◽  
Serum Vitamin ◽  
Vitamin B12 Deficiency ◽  
Vegetarian Diet ◽  
Vitamin B ◽  
Papio Cynocephalus ◽  
Experimental Production ◽  
Deficient Diet ◽  
Liver Vitamin

1. The development of vitamin B12 deficiency, as indicated by the serum and liver vitamin B12 levels and the excretion of methylmalonic acid, was studied over a 2-year period in baboons (Papio cynocephalus) given a diet deficient in vitamin B12. The effects of partial hepatectomy and the inclusion of either ampicillin or sodium propionate in the diet on the rate of development of the deficiency were also studied.2. The baboons had previously been fed on a mainly vegetarian diet. Their serum vitamin B12 levels were less than 100 ng/l and the mean liver vitamin B12 concentration was 0·56 μ/g. Similar serum and liver vitamin B12 levels were found in baboons given a purified diet supplemented with 1 μg vitamin B12/d, and marked increases in the serum and liver vitamin B12 levels occurred when the daily intake was increased to 2 μg.3. The serum vitamin B12 levels decreased to less than 20 ng/l in all baboons given a vitamin B12-deficient diet.4. The liver vitamin B12 concentration also decreased in all baboons given a deficient diet. At 9 months the lowest levels (0·20 μ/g) were found in partially hepatectomized baboons but subsequently baboons given the diet containing ampicillin had the lowest levels (0·11 μ/g).5. The excretion of methylmalonic acid after a valine load was found to be inversely related to the liver vitamin B12 concentration. In the early part of the study, partially hepatectomized baboons excreted the highest amount but subsequently baboons given a diet containing ampicillin excreted the highest amount.6. Increased formiminoglutamic acid excretion after a histidine load was observed in two baboons given a vitamin B12-deficient diet and in both baboons the liver folic acid concentration was low.7. No haematological or neurological symptoms of the vitamin B12 deficiency were observed.

Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Olaf Stanger ◽  
Martin Weger ◽  
Rima Obeid ◽  
Werner Temmel ◽  
Andreas Meinitzer ◽  
...  
Keyword(s):  
Optic Neuropathy ◽  
Methylmalonic Acid ◽  
Vascular Occlusion ◽  
Vitamin B ◽  
Ischemic Optic Neuropathy ◽  
Plasma Thcy ◽  
Retinal Vascular Occlusion ◽  
Total Homocysteine ◽  
Atherothrombotic Disease ◽  
Mild Hyperhomocysteinemia

AbstractMild hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as retinal vascular occlusion and non-arteritic ischemic optic neuropathy (NAION). Low intake or low status of B-vitamins explains elevated total homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy, methylmalonic acid (MMA) and cystathionine provide more information on the causes of impaired homocysteine metabolism as compared with vitamin B

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 Evaluation of the cobalt requirement of beef cattle based on vitamin B12, folate, homocysteine and methylmalonic acid

2000 ◽  
Vol 84 (5) ◽  
pp. 645-653 ◽  
Author(s):  
G. I. Stangl ◽  
F. J. Schwarz ◽  
H. Müller ◽  
M. Kirchgessner
Keyword(s):  
Linear Model ◽  
Methylmalonic Acid ◽  
Plasma Concentrations ◽  
Haemoglobin Concentration ◽  
Response Criterion ◽  
Quadratic Model ◽  
Vitamin B ◽  
Plasma Vitamin ◽  
Line Model ◽  
Growing Cattle

This investigation was designed to estimate the Co requirement of growing cattle on the basis of plasma and liver levels of vitamin B12 and folate, plasma levels of homocysteine and methylmalonic acid (MMA) and haematological variables. For this purpose thirty-four male intact cattle of the German Simmental breed (236 kg) were assigned randomly to ten groups and were fed corn silage-based diets which contained 70, 90, 109, 147, 184, 257, 327, 421, 589 or 689 μg Co/kg DM for 40 weeks. One-slope broken-line model analysis and a quadratic model with plateau were used to estimate the Co requirement. The broken-line model estimated the dietary Co requirement of growing cattle to be 257 (SE 29) ΜG/KG DIETARY DM BASED ON PLASMA VITAMIN B12 AS RESPONSE CRITERION. THE DIETARY CO LEVELS NEEDED TO MAXIMISE THE LIVER VITAMIN B12 AND LIVER FOLATE WERE 236 (se 8) and 190 (se 8) μg/kg dietary DM respectively. Plasma folate did not show any response to the different Co levels. The dietary Co was inversely correlated with the plasma concentrations of homocysteine and MMA. Estimates of the dietary Co concentration required to minimise homocysteine were 161 (se 10) μg/kg DM. When MMA was used as response criterion, the linear model yielded a Co requirement of 124 (se 3) μg/kg dietary DM. The quadratic model did not provide a better closeness of regression fit and yielded similar requirements to the linear model. Haemoglobin concentration and haematocrit tended to have a slight response to increasing dietary Co and were only decreased in cattle on diets containing less than 100 μg Co/kg DM. On the basis of the present data, recommended levels of dietary Co for normal folate metabolism and minimum homocysteine and MMA levels can be set to be 150–200 μg/kg DM; for maximum vitamin B12 levels, the desired Co content in the diet seems to be 250 μg/kg DM.

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